EP2516423A1 - Thiénylpyri(mi)dinylazole et utilisation associée dans la lutte contre des champignons phytopathogènes - Google Patents

Thiénylpyri(mi)dinylazole et utilisation associée dans la lutte contre des champignons phytopathogènes

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Publication number
EP2516423A1
EP2516423A1 EP10790993A EP10790993A EP2516423A1 EP 2516423 A1 EP2516423 A1 EP 2516423A1 EP 10790993 A EP10790993 A EP 10790993A EP 10790993 A EP10790993 A EP 10790993A EP 2516423 A1 EP2516423 A1 EP 2516423A1
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European Patent Office
Prior art keywords
alkyl
butyl
cyano
methyl
iso
Prior art date
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EP10790993A
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German (de)
English (en)
Inventor
Alexander Sudau
Mazen Es-Sayed
Catherine Sirven
Jürgen BENTING
Christoph Andreas Braun
Ruth Meissner
Anne-Sophie Rebstock
Samir Bennabi
Philippe Desbordes
Arounarith Tuch
Philippe Rinolfi
Stephane Brunet
Hiroyuki Hadano
Marie-Claire Grosjean-Cournoyer
Julia Neumann
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Bayer CropScience AG
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Bayer CropScience AG
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Priority to EP10790993A priority Critical patent/EP2516423A1/fr
Publication of EP2516423A1 publication Critical patent/EP2516423A1/fr
Withdrawn legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Definitions

  • the invention relates to novel Thienylpyri(mi)dinylazole and their agrochemically active salts, to their use and to methods and compositions for controlling phytopathogenic harmful fungi in and/or on plants or in and/or on seed of plants and for reducing mycotoxins in plants and parts of the plants, to processes for preparing such compounds and compositions and treated seed and also to their use for controlling phytopathogenic harmful fungi in agriculture, horticulture, forestry, in animal husbandry, in the protection of materials, in the domestic and hygiene field and for the reduction of mycotoxins in plants and parts of the plants.
  • the invention provides compounds of the formula (I),
  • R 1 represents Ci-C6-alkyl, C 2 -C6-alkenyl, C 2 -C6-alkinyl, Ci-C6-alkoxy, C3-C6-cycloalkyl, C3- Cg-allenyl, C3-Cg-trialkylsilyl, C4-Cg-cycloalkenyl ; Ci-C6-alkoxy-Ci-C6-alkyl, acyloxy-Cp Ce-alkyl, heteroaryl-C r C 6 -alkyl, aryl-C r C 6 -alkyl, Ci-C 6 -alkylthio-Ci-C 6 -alkyl, C r C 4 - alkyl-C(0)-Ci-C 6 -alkyl, C 3 -C 6 -cycloalkyl-C(0)-Ci-C4-alkyl, heterocyclyl-C(0)-Ci-C 4 - alkyl, Ci-
  • R 2 represents H, cyano, halogen or represents Ci-C6-alkyl, C3-C6-cycloalkyl, heterocyclyl, C 2 -Cg-alkenyl, C 2 -Cg-alkinyl, CpCg-alkoxy, C 2 -Cg-alkynyloxy, CpCg-alkylthio, C3-Cg-trialkylsilyl, each of which is optionally mono- or polysubstituted by identical or different substituents from the group consisting of halogen, cyano, amino, dimethylamino or methoxy and furthermore represents C 6 -Ci4-aryl which is optionally mono- or polysubstituted by identical or different substituents from the group consisting of halogen, cyano, Ci-C6-alkyl, Ci-C 6 -alkylamino, C r C 6 -dialkylamino, NH 2 , heterocyclyl, C(0)OC
  • R 8 represents H, halogen, cyano, Ci-C6-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl, C2-C6-alkinyl, C6-Cio-aryl, heteroaryl, heterocyclyl, or R 7 and R 8 together can form a 5- to 7-membered ring which can optionally be substituted with one or more substituents selected from: Ci-C palkyl, Ci-C/phalogenoalkyl, C1-C4- alkoxy, Ci-C4-halogenoalkoxy, halogen, hydroxyl, amino, cyano or nitro, whereas the cycle consists of carbon atoms but may also contain 1 to 4 heteroatoms selected from oxygen, sulphur or NR 19 , R 9 and R 10 represent H, C(S)R 14 , C(0)R 14 , S0 2 R 14 , C(0)OR 14 , OR 14 oder C(0)NR 14 R 15 or represent Ci-C6-al
  • R 11 and R 20 represent H, C(S)R 12 , C(0)R 12 , S0 2 R 12 , C(0)OR 12 , OR 12 or C(0)NR 12 R or represents Ci-C6-alkyl, C2-C6-alkenyl, C2-C6-alkinyl, C3-Cg-cycloalkyl, C6-Ci4-aryl, heterocyclyl or heteroaryl, each of which is optionally mono- or polysubstituted by identical or different substituents from the group consisting of F, CI, Br, OH, cyano, C1-C6- alkyl, 0-C(0)R 17 , 0-P(0)(OR 17 ) 2 , 0-B(OR 17 ) 2 or 0-(C r C 4 -alkyl),
  • R and R represent H
  • Ci-C6-alkyl C3-C6-cycloalkyl, C2-C6-alkenyl, C2-C6-alkinyl, C3-Cg-cycloalkyl, C6-Ci 4 -aryl, heterocyclyl oder heteroaryl, each of which is optionally mono- or polysubstituted by identical or different substituents from the group consisting of F, CI, Br, I, OH, carbonyl, cyano, Ci-C6-alkyl or Ci-C 4 -alkoxy,
  • R 14 and R 15 represent H
  • Ci-C6-alkyl C 3 -C6-cycloalkyl, C 2 -C6-alkenyl, C 2 -C6-alkinyl, C 3 -Cg-cycloalkyl, C6-Ci 4 -aryl, heterocyclyl oder heteroaryl, each of which is optionally mono- or polysubstituted by identical or different substituents from the group consisting of F, CI, Br, I, OH, cyano, methoxy, nitro, trifluormethyl, difluormethyl and furthermore represent C 3 -Cg-cycloalkyl-Ci-C6-alkyl , C6-Ci 4 -aryl-Ci-C6-alkyl, heterocyclyl-Ci-C6-alkyl, or heteroaryl-Ci-C6-alkyl, each of which is optionally mono- or polysubstituted by identical or different substituents from the group consisting of F, CI, Br,
  • R 16 represents OH, F, CI, Br, I, cyano, NH-C(0)R 17 , NR 17 R 18 , C(0)R 17 , C(0)OR 17 , C(0)NR 17 R 18 , S0 2 R 17 , OC(0)R 17 or represents Ci-C6-alkyl, C 2 -C6-alkenyl, C 2 -C6-alkinyl, C 3 -Cg-cycloalkyl, Ci-C 4 -alkoxy, S- (Ci-C 4 -alkyl), 0-(C 3 -C 8 -cycloalkyl), S-(C 3 -C 8 -cycloalkyl), C 6 -Ci 4 -aryl, 0-(C 6 -Ci 4 -aryl), S- (C6-Ci 4 -aryl), heterocyclyl or heteroaryl, each of which is optionally mono- or polysubstituted by identical or different substituents from the group consisting of F,
  • R 17 and R 18 represents Ci-C6-alkyl, C 3 -C6-cycloalkyl, C 2 -C6-alkenyl, C 2 -C6-alkinyl, benzyl, each of which is optionally mono- or polysubstituted by identical or different substituents from the group consisting of F, CI, Br, OH, cyano or represents H, or represents aryl, R iy represents H, C C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkinyl, C(S)R 14 , C(0)R 14 , S0 2 R 14 , C(0)OR 14 , and also agrochemically active salts thereof, whereas
  • the invention also provides the use of the compounds of the formula (I) as fungicides.
  • Thienylpyri(mi)dinylazole of the formula (I) according to the invention and also their agrochemically active salts are highly suitable for controlling phytopathogenic harmful fungi and for the reduction of mycotoxins.
  • the compounds according to the invention mentioned above have in particular strong fungicidal activity and can be used both in crop protection, in the domestic and hygiene field, in the protection of materials and for the reduction of mycotoxins in plants and parts of the plants.
  • the compounds of the formula (I) can be present both in pure form and as mixtures of various possible isomeric forms, in particular of stereoisomers, such as E and Z, threo and erythro, and also optical isomers, such as R and S isomers or atropisomers, and, if appropriate, also of tautomers.
  • stereoisomers such as E and Z, threo and erythro, and also optical isomers, such as R and S isomers or atropisomers, and, if appropriate, also of tautomers.
  • optical isomers such as R and S isomers or atropisomers
  • R 11 and R 20 represent H, C(S)R 12 , C(0)R 12 , S0 2 R 12 , C(0)OR 12 , OR 12 oder C(0)NR 12 R 13 or represent methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n- pentyl, 0-C(0)Me, 0-C(0)Et, 0-P(0)(OMe) 2 , 0-B(OMe) 2 , 0-B(OEt) 2 oder , methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, tert-butoxy substituted methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, cyclopropyl, cycl
  • R 12 and R 13 represent H
  • X 1 represents CH
  • N represents H, methyl, ethyl, propan-2-yl, isobutyl, butan-2-yl, 2-methylpropyl, prop-2-in-l- yl, 3-methylbut-2-en-l-y 1 , 4-methylpentan-2-yl, 3-methylbutyl, 2 , 2-dimethylpropyl, pentan-3-yl, terbutyl, 4-methylpentan-2-yl, , 3-dimethylbutan-2-yl, 3-methylbutan-2-yl, 2,2,2-trifluoroethyl, 2-chloro ethyl, 2-fluoroethyl, 2-methoxyethyl, methoxymethyl, 1- methoxypropan-2-yl, 2-(trifluormethoxy)ethyl, cyanomethyl, benzyl, 2-phenylethyl, - CH 2 C(0)OEt, tetrahydrofuran-2-ylmethyl,
  • X 1 represents CH, N, R 1 represents propan-2-yl, butan-2-yl, 2-methylpropyl, prop-2-in-l-yl, cyclopropyl,cyclobutyl, cyclopentyl, 2,2,2-trifluorethyl, 2-fluorobenzyl, 2-(trifluormethoxy)ethyl, 2-fluoroethyl, ethyl, but-l-en-3-yl, cyanomethyl, 3-pentyl, 2-chloroethyl, methoxymethyl, 2-cyanoethyl, 2,2-difluoroethyl, 2-ethoxyethyl, cyclopropylmethyl, 2-cyanobenzyl, 2,3-difluorobenzyl, methyl, R 2 represents H, methyl, prop- 1-ynyl,
  • R 3 represents H, acetylamino, n-propionylamino, isobutyrylamino,
  • R 4 represents H
  • R 5 represents H
  • R 6 represents CI, F
  • R 7 represents H
  • R 8 represents H and also agrochemically active salts thereof.
  • R 1 represents Propan-2-yl, Butan-2-yl, 2-Methylpropyl, Cyclobutyl, Cyclopentyl, But-l-en-3- yl, 2-Fluoroethyl, methyl, ethyl, where the other substituents have one or more of the meanings mentioned above, and to the agrochemically active salts thereof.
  • Very particular preference is furthermore given to compounds of the formula (I) in which
  • R 2 represents H, methyl, where the other substituents have one or more of the meanings mentioned above, and to the agrochemically active salts thereof.
  • R 3 represents NHCO-methyl, NHCO-isopropyl, NHCO-cyclopropyl, NHCO-ethyl, NHCO- cyclobutyl, NHCO-methoxymethyl, NHCO-methylcyclopropyl, NHCO-(2-methylpropyl), NHCO-(l-hydroxyethyl), N(CO-methyl)CO-methyl, NH 2 , NH-(3-oxetanyl) where the other substituents have one or more of the meanings mentioned above, and to the agrochemically active salts thereof.
  • R 3 represents NHCO-methyl, NHCO-isopropyl, NHCO-cyclopropyl, NHCO-ethyl, NHCO- cyclobutyl, NHCO-methoxymethyl, NHCO-methylcyclopropyl, NHCO-(2-methylpropyl), NHCO-(l-hydroxyethyl), N(CO-methyl)CO-
  • R 4 represents H, where the other substituents have one or more of the meanings mentioned above, and to the agrochemically active salts thereof.
  • the compounds of the formula (I) have acidic or basic properties and can form salts, if appropriate also inner salts, or adducts with inorganic or organic acids or with bases or with metal ions. If the compounds of the formula (I) carry amino, alkylamino or other groups which induce basic properties, these compounds can be reacted with acids to give salts, or they are directly obtained as salts in the synthesis. If the compounds of the formula (I) carries hydroxyl, carboxyl or other groups which induce acidic properties, these compounds can be reacted with bases to give salts.
  • Suitable bases are, for example, hydroxides, carbonates, bicarbonates of the alkali metals and alkaline earth metals, in particular those of sodium, potassium, magnesium and calcium, furthermore ammonia, primary, secondary and tertiary amines having groups, mono-, di- and trialkanolamines of (Cp C4)-alkanols, choline and also chlorocholine.
  • the salts obtainable in this manner also have fungicidal, herbicidal and insecticidal properties.
  • inorganic acids examples include hydrohalic acids, such as hydrogen fluoride, hydrogen chloride, hydrogen bromide and hydrogen iodide, sulphuric acid, phosphoric acid and nitric acid, and acidic salts, such as NaHSC>4 and KHSO 4 .
  • Suitable organic acids are, for example, formic acid, carbonic acid and alkanoic acids, such as acetic acid, trifluoroacetic acid, trichloroacetic acid and propionic acid, and also glycolic acid, thiocyanic acid, lactic acid, succinic acid, citric acid, benzoic acid, cinnamic acid, oxalic acid, alkylsulphonic acids (sulphonic acids having straight-chain or branched alkyl radicals of 1 to 20 carbon atoms), arylsulphonic acids or aryldisulphonic acids (aromatic radicals, such as phenyl and naphthyl, which carry one or two sulphonic acid groups), alkylphosphonic acids (phosphonic acids having straight-chain or branched alkyl radicals of 1 to 20 carbon atoms), arylphosphonic acids or aryldiphosphonic acids (aromatic radicals, such as phenyl and naphthyl, which carry one or two phospho
  • Suitable metal ions are in particular the ions of the elements of the second main group, in particular calcium and magnesium, of the third and fourth main group, in particular aluminium, tin and lead, and also of the first to eighth transition group, in particular chromium, manganese, iron, cobalt, nickel, copper, zinc and others. Particular preference is given to the metal ions of the elements of the fourth period.
  • the metals can be present in various valencies that they can assume.
  • Optionally substituted group s may b e mono- or polysubstituted, where in the case of polysubstitution the substituents may be identical or different.
  • halogen fluorine, chlorine, bromine and iodine
  • alkoxy saturated, straight-chain or branched alkoxy radicals having 1 to 8 carbon atoms, for example (but not limited thereto) Ci-C6-alkoxy, such as methoxy, ethoxy, propoxy, 1- methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, 1,1-dimethylethoxy, pentoxy, 1- methylbutoxy, 2-methylbutoxy,
  • 5-membered heteroaryl which contains one to four nitrogen atoms or one to three nitrogen atoms and one sulphur or oxygen atom
  • 5-membered heteroaryl groups which, in addition to carbon atoms, may contain one to four nitrogen atoms or one to three nitrogen atoms and one sulphur or oxygen atom as ring members, for example (but not limited thereto) 2-furyl, 3-furyl, 2- thienyl, 3-thienyl, 2-pyrrolyl, 3-pyrrolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 3-isothiazolyl, 4- isothiazolyl, 5-isothiazolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 5- oxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-imidazolyl, 4-imidazolyl, l ,
  • 5-membered heteroaryl which is attached via nitrogen and contains one to four nitrogen atoms, or benzo-fused 5-membered heteroaryl which is attached via nitrogen and contains one to three nitrogen atoms: 5-membered heteroaryl groups which, in addition to carbon atoms, may contain one to four nitrogen atoms and one to three nitrogen atoms, respectively, as ring members and in which two adjacent carbon ring members or a nitrogen and an adjacent carbon ring member may be bridged by a buta-l,3-dien-l,4-diyl group in which one or two carbon atoms may be replaced by nitrogen atoms, where these rings are attached to the skeleton via one of the nitrogen ring members, for example (but not limited thereto) 1-pyrrolyl, 1-pyrazolyl, 1 ,2,4-triazol-
  • 6-membered heteroaryl which contains one to four nitrogen atoms: 6-membered heteroaryl groups which, in addition to carbon atoms, may contain one to three or one to four nitrogen atoms as ring members, for example (but not limited thereto) 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 3- pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 1,3,5-triazin-
  • the present invention furthermore relates to a process for preparing thienylpyrazoles of the formula (I) according to the invention.
  • a general summary of the synthesis paths is shown in Schemes 1 to 8.
  • a compound of the general formula (IVa) can be reacted with a compound of the formula (V) to give a compound of formula (Ilia) (Scheme 1).
  • This compound can be subjected to a reaction with a formylating agent to afford a compound of general formula (Ila).
  • the compound of formula (Ip) where R 3b is a leaving group can be submitted to nucleophilic substitution or Buchwald coupling to give the amino derivative of formula (Ic) (Scheme 3).
  • R 10 H (lea) this compound can be further subjected to alkylation or acylation to afford the compound of general formula (Icb).
  • R 3c is a protected amino group (Ice) this compound can be deprotected to afford the corresponding amine of the general formula (led) (Scheme 3) which can be further subjected to alkylation and/or acylation or subjected to sulfonyl chloride, carbamoyl chloride, isocyanate to afford the compound of general formula (Ice).
  • the compound of formula (Ip) where R 3b is a leaving group can also be subjected to various transition metal catalysed C-C coupling to afford (Ig) (Scheme 4).
  • the compound of formula (Iq) where R 6a is an halogen can be subjected to transition metal catalysed C- C coupling to afford the compound of formula (Im). Alternatively, it can be subjected to metallation to generate an organometallic which could then be trapped by an electrophile to afford the compound of formula (Im). (Scheme 6).
  • R 3 halogen, OTf, S(0) 2 Me
  • R 3c protected amino group (acetylamino, benzylamino, diphenylmethyleneamino)
  • R 3b halogen, OTf, S(0) 2 Me
  • R3d cyano, alkynyl, amide, alkyl, cydoalkyi, aryl, alkenyl, heteroaryl, dialkylamide, alkylamide
  • R 2a halogen
  • R 2 alkyl, cydoalkyi, alkynyl, cyano, alkylthio, trialkylsilyl, halogen, alkenyl
  • R 6a halogen
  • R 6 alkyl, cycloalkyl, alkynyl, cyano, alkenyl, amide, aryl, heteroaryl, alkylthio, halogen, trialkylsilyl
  • Halogenation of this compound can give the halogenated compound of formula (VIII) (Scheme 7) which can be subjected to a transition metal catalysed cross coupling with the compound of formula (XII) to afford the bisarylpyrazole of general formula (Iz) (Scheme 7).
  • the compound of general formula (Iz) can be prepared by a cross coupling reaction between the compound of general formula (VI) and the organometallic compound (VII) (Scheme 7) which can be generated from the halogeno compound (VIII) (Scheme
  • Another possibility can be to start with the bromopyrazole (XVII).
  • the protection of this compound can afford the compound of formula (XVI) which can then be subjected to a transition metal catalysed cross coupling with the compound of formula (XII) to give the arylpyrazole of formula (XV) (Scheme 8).
  • This compound can be metallated to afford the organometallic (XIV) which could then undergo a cross coupling reaction with the compound of general formula (XIII) to give the compound of formula (Io) where R 1 is a protecting group, PG 2 (Scheme 8).
  • R 2e represents optionnally substituted Ci-Ce-alkyl, Ci-C6-haloalkyl, OH, Ci-C6-alkoxy, C3-C6- cycloalkyl, heterocyclyl, C 2 -C 6 -alkenyl, C r C 6 -alkylC(0)OCi-C 6 -alkyl, C r C 6 -alkyl- OC(0)C r C 6 -alkyl, tri(C r C 6 -alkyl)silyl, C 6 -Ci 4 -aryl, C 6 -Ci 4 -heteroaryl, R la represents Ci-C6-alkyl and Ci-C6-haloalkyl, as well as salts thereof,
  • R la preferebly represents methyl, ethyl, propan-2-yl, butan-2-yl, pentan-3-yl, 2-methylpropyl, 2,2-difluoroethyl, R 2e preferably represents H or methyl,
  • R 1 and R 2c have the above-mentioned meaning, as well as salts thereof,
  • R 2c preferably represents H or methyl, Thienylpyrazole-derivatives of the formula (VII),
  • R 1 , R 6 , R 7 ,R 8 , B, R 2c have the above-mentioned as well as salts thereof, R 2c preferably represents H or methyl, excluded are compounds with R 1 equals trityl.
  • Process A Compounds of the general formula (la) may be obtained, according to known literature methods (US 6,335,336 A; Journal of Medicinal Chemistry, 2003, 46, 5416-5427), by reacting a compound of general formula (Ila) with a hydrazine of general formula R 1 -NH-NH 2 or a hydrated form thereof.
  • Inert solvent such as cyclic or acyclic ethers (e.g. diethyl ether, tetrahydrofuran, dioxane), alcohols (e.g. methanol or ethanol) can be used.
  • the reaction can be carried out in mixtures of two or more of these solvents.
  • a base e.g. triethylamine may be used if desired.
  • the reaction temperature can be varied from 10 °C to 50 °C but room temperature is preferred.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the reaction can be performed in a microwave apparatus (e.g. CEM Explorer) at elevated temperature, which may shorten the reaction time.
  • compounds (la) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography.
  • Compounds of the general formula (Ila) may be obtained, according to known literature methods (J. Med. Chem 2007, 50, 2732-2736; Journal of Heterocyclic Chemistry, 2008, 45, 1819-
  • a compound of general formula (Ilia) by reacting a compound of general formula (Ilia) with a formylating agent such as an alkyl formiate (e.g. methyl formiate), a trialkyl orthoformiate (e.g. trimethyl orthoformiate) or an acetal of ⁇ , ⁇ -dialkylformamide.
  • a solvent is used optionally. Typical solvents include alcohols (e.g. ethanol), esters (e.g. ethyl acetate), ethers (e.g. THF) and also more polar solvents such as DMF or NMP.
  • the reaction temperature can be varied from room temperature to the boiling point of the reaction mixture.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • compounds (Ila) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography, or they can, if appropriate, also be used for the next step without prior purification.
  • Compounds of the general formula (Ilia) may be prepared, according to known literature methods (J. Med. Chem. 2007, 50, 2732-2736 and WO 05/040155) by reacting a compound of the general formula (IVa) with an ester, dialkylamide or N,0-dialkylamide of general formula (V) under the influence of a strong base.
  • Typical bases used in this reaction are alkoxides (e.g. potassium tert-butoxide or sodium tert- butoxide), lithium amides (e.g. LDA or LiHMDS) and metal hydride (e.g. potassium or sodium hydride).
  • Typical solvents are ethers (e.g. diethylether, glyme and THF). In certain cases the use of more polar solvents (e.g. DMF, DMSO and HMPT) is preferred.
  • the reaction can be carried out in mixtures of two or more of these solvents.
  • the preferred solvent is tetrahydrofuran.
  • the starting materials are employed in equimolar amounts.
  • the reaction is usually carried out at temperatures of -78 °C to the boiling point of the solvent and preferably at 0 °C - 25 °C.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • compounds (Ilia) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography, or they can, if appropriate, also be used for the next step without prior purification.
  • These compounds may also be obtained by nucleophilic substitution using e.g. MeMgCl (as described in WO 06/054151 ), or palladocatalysed coupling using e.g. MeB(OH) 2 (as described in WO 05/028434).
  • R 3d halogen
  • R 9c , R 10c optionnally substituted alkyl or cycloalkyl
  • compounds of formula (IIIc) may also be prepared by nucleophilic substitution which means by direct treatment of compounds of formula (Illaa), where R 3d represents a leaving group such as chlorine with an amine of general formula HNR 9c R 10c under thermal or microwave conditions, if appropriate in the presence of a solvent and if appropriate in the presence of a base.
  • solvents are all customary solvents which are inert under the reaction conditions, such as cyclic and acyclic ethers (e.g. diethyl ether, tetrahydrofuran, dioxane), aromatic hydrocarbons (e.g.
  • benzene, toluene, xylene halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride), halogenated aromatic hydrocarbons (e.g. chlorobenzene, dichlorobenzene), amides (e.g. ⁇ , ⁇ -dimethylformamide) and nitriles (e.g. acetonitrile), or the reaction can be carried out in mixtures of two or more of these solvents. Preferrably the reaction can be performed without solvent.
  • halogenated hydrocarbons e.g. dichloromethane, chloroform, carbon tetrachloride
  • halogenated aromatic hydrocarbons e.g. chlorobenzene, dichlorobenzene
  • amides e.g. ⁇ , ⁇ -dimethylformamide
  • nitriles e.g. acetonitrile
  • the reaction is usually carried out at temperatures of 20 °C - 160 °C and preferably at 110 °C in the microwave oven.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • compound (IIIc) is removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography.
  • the alkylation can be performed with an alkylating agent of formula R'-LG 1 (where LG 1 is a leaving group such as halogen, inflate, mesylate) in the presence of a base.
  • Suitable for use as solvents are all customary solvents which are inert under the reaction conditions, such as cyclic and acyclic ethers (e.g. diethyl ether, tetrahydrofuran, dioxane), aromatic hydrocarbons (e.g. benzene, toluene, xylene), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride), halogenated aromatic hydrocarbons (e.g.
  • chlorobenzene dichlorobenzene
  • amides e.g. ⁇ , ⁇ -dimethylformamide
  • nitriles e.g. acetonitrile
  • the preferred solvents are ⁇ , ⁇ -dimethylformamide and acetonitrile.
  • At least one equivalent of base e.g. cesium carbonate or sodium hydride
  • the reaction is usually carried out at temperatures of 0 °C - 100 °C and preferably at 20 °C - 30 °C, but it can also be carried out at the reflux temperature of the reaction mixture.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the compounds (I) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography.
  • the acylation is performed in the presence of an acylating agent such as R 17 C(0)C1 in the presence of an acid scavenger/base.
  • Suitable for use as solvents are all customary solvents which are inert under the reaction conditions, such as, for example, cyclic and acyclic ethers (e.g. diethyl ether, tetrahydrofuran, dioxane), aromatic hydrocarbons (e.g. benzene, toluene, xylene), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride), halogenated aromatic hydrocarbons (e.g. chlorobenzene, dichlorobenzene) and nitriles (e.g. acetonitrile), or the reaction can be carried out in mixtures of two or more of these solvents.
  • the preferred solvents are tetrahydrofuran and dichloromethane.
  • At least one equivalent of an acid scavenger / a base e.g. Hiinig base, triethylamine or commercially available polymeric acid scavengers
  • a base e.g. Hiinig base, triethylamine or commercially available polymeric acid scavengers
  • the starting material is a salt, at least two equivalents of the acid scavenger are required.
  • the reaction is usually carried out at temperatures of 0 °C - 100 °C and preferably at 20 °C - 30 °C, but it can also be carried out at the reflux temperature of the reaction mixture.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the compounds (I) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography.
  • R 1 contains a carbonyl function, it can be subjected to thionation in the presence of a thionating agent like for example sulphur (S), sulfhydric acid (H 2 S), sodium sulfide (Na 2 S), sodium hydrosulfide (NaHS), boron trisulfide (B 2 S 3 ), bis (diethylaluminium) sulfide ((AlEt 2 ) 2 S), ammonium sulfide ((NH 4 ) 2 S), phosphorous pentasulfide (P 2 S 5 ), Lawesson's reagent (2,4-bis(4- methoxyphenyl)-l,2,3,4-dithiadiphosphetane 2,4-disulfide) or a polymer-supported thionating reagent such as described in J.ChemSoc. Perkin 1, (2001), 358.
  • S sulphur
  • H 2 S sulf
  • Suitable for use as solvents are all customary solvents which are inert under the reaction conditions, such as cyclic and acyclic ethers (e.g. diethyl ether, tetrahydrofuran, dioxane), aromatic hydrocarbons (e.g. benzene, toluene, xylene), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride), halogenated aromatic hydrocarbons (e.g. chlorobenzene, dichlorobenzene) and the reaction can be carried out in mixtures of two or more of these solvents.
  • the preferred solvent is dichloromethane.
  • the reaction temperature is in the range of 50 °C to the boiling point of the reaction mixture.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the reaction can be performed in a microwave apparatus (e.g. CEM Explorer) at elevated temperature, which may shorten the reaction time.
  • compounds (I) are isolated from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography.
  • the compounds of the general formula (Ih) can be synthesized from corresponding compounds (Iba) as shown in scheme 5 step j).
  • reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the compounds (Ic) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography.
  • Compounds of formula (Ic) may also be prepared by nucleophilic substitution which means by direct treatment of compounds of formula (Ip), where R 3b represents a leaving group such as chlorine with an amine of general formula HNR 9 R 10 under thermal or microwave conditions, if appropriate in the presence of a solvent and if appropriate in the presence of a base.
  • solvents are all customary solvents which are inert under the reaction conditions, such as cyclic and acyclic ethers (e.g. diethyl ether, tetrahydrofuran, dioxane), aromatic hydrocarbons (e.g. benzene, toluene, xylene), halogenated hydrocarbons (e.g.
  • dichloromethane chloroform, carbon tetrachloride
  • halogenated aromatic hydrocarbons e.g. chlorobenzene, dichlorobenzene
  • amides e.g. ⁇ , ⁇ -dimethylformamide
  • nitriles e.g. acetonitrile
  • the reaction can be carried out in mixtures of two or more of these solvents.
  • the reaction can be performed without solvent.
  • the reaction is usually carried out at temperatures of 20 °C - 160 °C and preferably at 140 °C in the microwave oven.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • compound (Ic) is removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography.
  • Suitable for use as solvents are all customary solvents which are inert under the reaction conditions, such as cyclic and acyclic ethers (e.g. diethyl ether, tetrahydrofuran, dioxane), aromatic hydrocarbons (e.g. benzene, toluene, xylene), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride), halogenated aromatic hydrocarbons (e.g. chlorobenzene, dichlorobenzene), amides (e.g. ⁇ , ⁇ -dimethylformamide) and nitriles (e.g. acetonitrile), or the reaction can be carried out in mixtures of two or more of these solvents.
  • the preferred solvents are ⁇ , ⁇ -dimethylformamide and acetonitrile.
  • the reaction is usually carried out at temperatures of 20 °C - 100 °C and preferably at 60 °C - 80 °C, but it can also be carried out at the reflux temperature of the reaction mixture.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the compounds (Icb) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography.
  • Suitable for use as solvents are all customary solvents which are inert under the reaction conditions, such as, for example, cyclic and acyclic ethers (for example diethyl ether, tetrahydrofuran, dioxane), aromatic hydrocarbons (for example benzene, toluene, xylene), halogenated hydrocarbons (for example dichloromethane, chloroform, carbon tetrachloride), halogenated aromatic hydrocarbons (for example chlorobenzene, dichlorobenzene) and nitriles (for example acetonitrile), or the reaction can be carried out in mixtures of two or more of these solvents.
  • cyclic and acyclic ethers for example diethyl ether, tetrahydrofuran, dioxane
  • aromatic hydrocarbons for example benzene, toluene, xylene
  • halogenated hydrocarbons for example dichloromethane, chloro
  • the preferred solvents are tetrahydrofuran and dichloromethane.
  • At least one equivalent of an acid scavenger / a base for example pyridine is employed, based on the starting material of the general formula (lea). If the starting material is a salt, at least two equivalents of the acid scavenger are required.
  • the reaction is usually carried out at temperatures of 0 °C - 100 °C and preferably at 20 °C - 30 °C, but it can also be carried out at the reflux temperature of the reaction mixture.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the compounds (Icb) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography.
  • R 9 and/or R 10 contain a carbonyl function, it can be subjected to thionation in the presence of a thionating agent like for example sulphur (S), sulfhydric acid (H 2 S), sodium sulfide (Na 2 S), sodium hydrosulfide (NaHS), boron trisulfide (B 2 S 3 ), bis (diethylaluminium) sulfide ((AlEt 2 ) 2 S), ammonium sulfide ((NH 4 ) 2 S), phosphorous pentasulfide (P 2 S 5 ), Lawesson's reagent (2,4-bis(4- methoxyphenyl)-l,2,3,4-dithiadiphosphetane 2,4-disulfide) or a polymer-supported thionating reagent such as described in J.ChemSoc. Perkin 1, (2001), 358.
  • S sulphur
  • the compounds (Ice) can be synthesized from corresponding compounds (led) where R 3 is a free amino group.
  • R 3 is a free amino group.
  • Compounds of formula (Ice) where R 3 is a protected amino function can be deprotected under state of the art methods depending on the nature of the protective group to generate the compound of formula (led) where R 3 is a free amine (see “Protective groups in organic chemistry” Green and Wuts 4 th edition, Wiley Interscience).
  • benzyl as protective group can be deprotected under acidic condition such as concentrated sulphuric acid or hydrogenation condition.
  • the intermediate (led) can be further alkylated or acylated using the same procedure as describe above to afford compounds of formula (Ice) where R 3 is NHR 9 a or NR 9a R 9a .
  • Another alkylation or acylation will provide, under the same conditions, compounds where R 3 is NR 9a R 10a as previously described.
  • M represents MgCl, MgBr, ZnCl, ZnBr, ZnCN, B(OH) 2 , BF 3 K, B(Ci-C 8 -alkoxy) 2 , SnMe 3 , SnBu 3 , CuCl, CuBr, CuCN, AgCl, AgBr.
  • Compound of the general formula R 3c -M can be either prepared in situ or prior to the reaction.
  • Suitable for use as solvents are all customary solvents which are inert under the reaction conditions, such as, for example, cyclic and acyclic ethers (for example diethyl ether, tetrahydrofuran, dioxane), aromatic hydrocarbons (for example benzene, toluene, xylene), halogenated hydrocarbons (for example dichloromethane, chloroform, carbon tetrachloride), carboxylic esters (for example ethyl acetate), amides (for example ⁇ , ⁇ -dimethylformamide, N,N- dimethylacetamide), dimethyl sulphoxide and l,3-dimethyl-2-imidazolinone, and the reaction can be carried out in mixtures of two or more of these solvents.
  • cyclic and acyclic ethers for example diethyl ether, tetrahydrofuran, dioxane
  • aromatic hydrocarbons for example benzene,
  • the reaction should be carried out in the presence of additives depending on the type of coupling that is performed. For example, if Sonogashira reaction is performed triethylamine (at least one equivalent based on the compound (Ip)) and copper(I) iodide (at least 0.1 equivalent based on the compound (Ip)) is added.
  • Suitable catalyst for carrying out the above mentioned process according to the invention may be chosen as being a metal salt or complex.
  • Suitable metal derivatives for this purpose are based on palladium.
  • Suitable metal salts or complexes for this purpose are palladium chloride, palladium acetate, tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium dichloride or 1 , 1 '-bis(diphenylphosphino) ferrocenepalladium(II) chloride.
  • a palladium complex in the reaction mixture by separate addition to the reaction of a palladium salt and a ligand or salt, such as a phosphine, for example triethylphosphine, tri-tert-butylphosphine, tricyclohexylphosphine, 2-(dicyclo- hexylphosphine)biphenyl, 2-(di-tert-butylphosphin)biphenyl, 2-(dicyclohexylphosphine)-2'-(N,N- dimethylamino)-biphenyl, triphenylphosphine, tris-(o-tolyl)phosphine, sodium 3- (diphenylphosphino)benzolsulfonate, tris-2-(methoxyphenyl)phosphine, 2,2'-bis-(diphenyl- phosphine)-l,l'-binaphthy
  • the amount of catalyst used is at least 1% to an excess based on the starting material (Ip).
  • the reaction is usually carried out at temperatures of 20 °C - 160 °C and preferably at 20 °C - 120 °C.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the reaction is generally carried out under atmospheric pressure but it is also possible to operate under elevated pressure.
  • the compounds (Ig) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography.
  • the compounds (Ij) can be synthesized from corresponding compounds (Ik), where R 2a is a leaving group, as shown in scheme 5 step 1).
  • R 3d halogen reactive intermediate
  • A) Compounds of formula (Ipa) where R 3d is bromide or chloride can be prepared by treating the corresponding N-oxide with POCI 3 or POBr 3 under conditions used in state of the art methodology (e.g. chlorination of substituted pyridines in Chem. and Pharm. Bull. 1994, 42(9), 1841).
  • Process E j) The intermediate (Iba) can be alkylated or acylated using the same procedures as described for Process B, step d) to afford compounds of formula (Ih).
  • Compounds of formula (Iba) may be obtained by deprotection of compounds of formula (Ij) under state of the art methods depending on the nature of the protective group.
  • paramethoxybenzyl as protective group can be deprotected under acidic condition such as TFA or hydrogenation condition (see “Protective groups in organic chemistry” Green and Wuts 4 th edition, Wiley Interscience). It is to be noted that weak deprotecting group may be deprotected during the course of the reaction.
  • compounds of general formula (Ij) with R 2b is halogen, trialkylsilyl, alkylthio or alkyl
  • a base e.g. n-butyllithium or isopropylmagnesium chloride
  • solvent e.g. diethyl ether or tetrahydrofurane
  • an electrophile e.g. trimethylsilyl chloride or dimethyldisulfide
  • the reaction is usually carried out at temperatures of -80 °C - 20 °C depending on the base used to perform the reaction. During the reaction a change in temperature may be beneficial or necessary to ensure the reaction with the second reactant.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the compounds (Ij) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography, or they can, if appropriate, also be used for the next step without prior purification.
  • the compounds (Im) can be synthesized from corresponding compounds (Iq), where R 6a is a leaving group, as shown in Scheme 6, step o).
  • m) Compounds of formula (Ik) (where PG 2 is a protective group such as paramethoxybenzyl or tetrahydropyranyl) may be obtained by protection of a compound of general formula (II) (see “Protective groups in organic chemistry” Green and Wuts 4 th edition, Wiley Interscience).
  • the intermediate of formula (II) with R 2a is halogen can be synthesized by halogenation of a compound of formula (Iaa) where R 2 and R 1 are hydrogen using a suitable halogenating agent in an appropriate solvent.
  • Suitable for use as solvents are all customary solvents which are inert under the reaction conditions, such as, for example, alcohols (e.g. methanol, ethanol, propanol), cyclic and acyclic ethers (e.g. diethyl ether, tetrahydrofuran, dioxane), aromatic hydrocarbons (e.g. benzene, toluene, xylene), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride), halogenated aromatic hydrocarbons (e.g. chlorobenzene, dichlorobenzene), carboxylic esters (e.g.
  • alcohols e.g. methanol, ethanol, propanol
  • cyclic and acyclic ethers e.g. diethyl ether, tetrahydrofuran, dioxane
  • aromatic hydrocarbons e.g. benzene, to
  • amides e.g. N,N-dimethylformamide, N,N-dimethylacetamide
  • dimethyl sulphoxide 1 ,3- dimethyl-2-imidazolinone
  • water and acetic acid or the reaction can be carried out in mixtures of two or more of these solvents.
  • Preferred solvents for this reaction is N,N-dimethylformamide.
  • Suitable for use as halogen source are, e.g., N-bromosuccinimide, N-chlorosuccinimide, N- iodosuccinimide, pyridinium tribromide, or bromine.
  • the reaction can, if appropriate, be carried out using an acid, such as for example acetic acid, sulphuric acid, hydrobromic acid or hydrochloric acid.
  • the starting materials and the halogenating agent are employed in equimolar amounts.
  • the halogenating agent can also be used in excess.
  • the reaction is usually carried out at temperatures of 0 °C - 60 °C and preferably at 0 °C - 30 °C, but it can also be carried out at the reflux temperature of the reaction mixture.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • Process F o) Compounds of formula (Im) with R 6b is alkynyl, alkenyl, cycloalkyl, alkyl, cyano, aryl, alkylsulfanyl, halogen or trialkylsilyl can be prepared using analoguous conditions as previously described for Process E, step 1) starting from compounds of general formula (Iq) with R 6a is an halogen.
  • R ft is cyano
  • the compound can be further modified by state of the art methods to generate all the possible derivatives of the cyanide group: e.g., hydrolysis to form the acid or amide, reduction to form the amine or aldehyde, addition on cyanide of an alkyl or aryl Grignard to generate the ketone.
  • Process G p) Compounds of general formula (Iz) can be obtained for example by coupling a compound of the general formula (VII) with heterocycles of the general formula (VI) (Scheme 7).
  • B represents e.g. a boronic ester (e.g. pinacol borane) or a boronic acid.
  • Z 3 represents a leaving group such as chlorine, bromine, iodine or OTf.
  • the reaction can be performed in the presence of a catalyst, a base and a suitable solvent at an appropriate temperature according to known literature procedures (Top Curr. Chem 2002, 219, 11, b - A. Suzuki, Org. Chem 1999, 28, 147 and literature cited therein).
  • Suitable catalyst for carrying out the above mentioned process may be chosen as being a metal salt or complex.
  • Suitable metal derivatives for this purpose are based on palladium.
  • Suitable metal salts or complexes for this purpose are palladium chloride, palladium acetate, tetrakis(triphenyl- phosphine)palladium, bis(triphenylphosphine)palladium dichloride or l ,l '-bis(diphenylphosphino) ferrocenepalladium(II) chloride.
  • a palladium complex in the reaction mixture by separate addition to the reaction of a palladium salt and a ligand or salt, such as a phosphine, for example triethylphosphine, tr i-tert-b utylphosphine, tricyclohexylphosphine, 2- (dicyclohexylphosphine)biphenyl, 2-(di-tert-butylphosphin)biphenyl, 2-(dicyclohexylphosphine)- 2'-(N,N-dimethylamino)-biphenyl, triphenylphosphine, tris-(o-tolyl)phosphine, sodium 3- (diphenylphosphino)benzolsulfonate, tris-2-(methoxyphenyl)phosphine, 2,2'-bis-(diphenyl- phosphine)-l,l'
  • the amount of catalyst used is at least 1% to an excess based on the starting material (VI).
  • the reaction is usually carried out at temperatures of 20 °C - 160 °C and preferably at 20 °C - 120 °C.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • reaction is generally carried out under atmospheric pressure but it is also possible to operate under elevated pressure.
  • the compounds (Iz) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography.
  • Suitable solvents for carrying out this reaction are customary inert organic solvents, such as Sulfoxides (e.g. dimethylsulfoxide), cyclic ethers (e.g. dioxane) and amides (e.g. N,N- dimethylformamide).
  • Sulfoxides e.g. dimethylsulfoxide
  • cyclic ethers e.g. dioxane
  • amides e.g. N,N- dimethylformamide.
  • the reaction can also be carried out in mixtures of two or more of these solvents.
  • the preferred solvents are dimethyl sulfoxide and dioxane.
  • the reaction is usually carried out at temperatures between 80 ° C and 120 ° C, the preferred reaction temperature is 85 ° C - 90 ° C.
  • the reaction time varies depending on the scale and temperature of the reaction, but is generally between one hour and 16 hours.
  • compounds of the formula (VII) can be prepared by metallation of bromopyrazole (VIII) with bases such as n-butyl lithium and reaction with trialky lb orate.
  • bases such as n-butyl lithium
  • the resulting boronic ester can be used as such in the coupling reaction, treated with diol like pinacol to afford the corresponding cyclic boronic ester (as described in J. Het. Chem, 2004, 41, 931-940, or EP-A 1 382 603) or hydro lysed following standard procedure to generate the corresponding boronic acid.
  • At least one equivalent of base e.g. butyl lithium or isopropylmagnesium chloride is employed, based on the starting material of the general formula (VIII).
  • the reaction is usually carried out at temperatures of -80 °C - 20 °C depending on the base used to perform the reaction. During the reaction a change in temperature may be beneficial or necessary to ensure the reaction with the second reactant.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the compounds (VII) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography, or they can, if appropriate, also be used for the next step without prior purification.
  • the intermediate of formula (VIII) can be synthesized by halogenation of a compound of formula (IXa) using a suitable halogenating agent in an appropriate solvent.
  • Suitable for use as solvents are all customary solvents which are inert under the reaction conditions, such as, for example, alcohols (e.g. methanol, ethanol, propanol), cyclic and acyclic ethers (e.g. diethyl ether, tetrahydrofuran, dioxane), aromatic hydrocarbons (e.g. benzene, toluene, xylene), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride), halogenated aromatic hydrocarbons (e.g. chlorobenzene, dichlorobenzene), carboxylic esters (e.g.
  • alcohols e.g. methanol, ethanol, propanol
  • cyclic and acyclic ethers e.g. diethyl ether, tetrahydrofuran, dioxane
  • aromatic hydrocarbons e.g. benzene, to
  • amides e.g. N,N-dimethylformamide, N,N-dimethylacetamide
  • dimethyl sulphoxide 1 ,3- dimethyl-2-imidazolinone
  • water and acetic acid or the reaction can be carried out in mixtures of two or more of these solvents.
  • Preferred solvents for this reaction is N,N-dimethylformamide.
  • Suitable for use as halogen source are, e.g., N-bromosuccinimide, N-chlorosuccinimide, N- iodosuccinimide, pyridinium tribromide, or bromine.
  • the reaction can, if appropriate, be carried out using an acid, such as for example acetic acid, sulphuric acid, hydrobromic acid or hydrochloric acid.
  • an acid such as for example acetic acid, sulphuric acid, hydrobromic acid or hydrochloric acid.
  • the starting materials and the halogenating agent are employed in equimolar amounts.
  • the halogenating agent can also be used in excess.
  • the reaction is usually carried out at temperatures of 0 °C - 60 °C and preferably at 0 °C - 30 °C, but it can also be carried out at the reflux temperature of the reaction mixture.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the compounds (IXa) can be prepared according to scheme 7. They are obtained by alkylation of compounds of formula (X). The reaction can be performed with an alkylating agent of formula Rl-Y (where Y is a leaving group such as halogen, inflate, mesylate and the like) in the presence of a base.
  • Suitable for use as solvents are all customary solvents which are inert under the reaction conditions, such as, for example, cyclic and acyclic ethers (e.g. diethyl ether, tetrahydrofuran, dioxane), aromatic hydrocarbons (e.g. benzene, toluene, xylene), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride), halogenated aromatic hydrocarbons (e. g. chlorobenzene, dichlorobenzene), amides (e.g. ⁇ , ⁇ - dimethylformamide) and nitriles (e.g.
  • cyclic and acyclic ethers e.g. diethyl ether, tetrahydrofuran, dioxane
  • aromatic hydrocarbons e.g. benzene, toluene, xylene
  • halogenated hydrocarbons
  • acetonitrile or the reaction can be carried out in mixtures of two or more of these solvents.
  • the preferred solvents are ⁇ , ⁇ - dimethylformamide and acetonitrile.
  • At least one equivalent of base e.g. cesium carbonate or sodium hydride is employed, based on the starting material of the general formula (X).
  • the reaction is usually carried out at temperatures of 0 °C - 100 °C and preferably at 20 °C - 30 °C, but it can also be carried out at the reflux temperature of the reaction mixture.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the compounds (IXa) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography, or they can, if appropriate, also be used for the next step without prior purification.
  • Compounds of the general formula (X) can be prepared according to known procedure (Tetrahedron, 2003, 59, 555-560) for example using acetylthiophenyl of general formula (XI) and react it with a substrate of general formula R 2c C(OR) 2 NMe 2 and subsequently with hydrazine. Alternatively it can be subjected to a substrate of general formula R 2c C(0)(OR) in the presence of a base (as described for example in WO2009158380 or in US200962252) and subsequently with hydrazine.
  • Acetylthiophenyl of general formula (XI) are commercially available or can be prepared for example by addition of Methylmagnesium bromide on the corresponding weinreb amide (as described in Bioorganic & Medicinal Chemistry Letters, 19(3), 1018-1021; 2009).
  • Compounds of the general formula (Iz) may alternatively be prepared according to scheme 7.
  • Compounds of the formula (Iz) can also be prepared by coupling the bromopyrazole (VIII) with metallated heterocycles of general formula (XII) where B represents trialkyltin such as for example tributyltin.
  • the reaction can be performed in the presence of a catalyst, and a ligand if appropriate and a suitable solvent at an appropriate temperature according to known literature procedures produce (Synthesis 1992, 803-815).
  • Suitable catalyst for carrying out the above mentioned processes according to the invention may be chosen as being a metal salt or complex.
  • Suitable metal derivatives for this purpose are based on palladium.
  • Suitable metal salts or complexes for this purpose are palladium chloride, palladium acetate, tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium dichloride or 1 , 1 '-bis(diphenylphosphino) ferrocenepalladium(II) chloride.
  • a palladium complex in the reaction mixture by separate addition to the reaction of a palladium salt and a ligand or salt, such as a phosphine, for example triethylphosphine, tri-tert-butylphosphine, tricyclohexylphosphine, 2-(dicyclo- hexylphosphine)biphenyl, 2-(di-tert-butylphosphin)biphenyl, 2-(dicyclohexylphosphine)-2'-(N,N- dimethylamino)-biphenyl, triphenylpho sphine, tris-(o-tolyl)phosphine, sodium 3-(di- phenylphosphino)benzolsulfonate, tris-2-(methoxyphenyl)phosphine, 2,2'-bis-(diphenylphosphine)- 1 , 1 '-bina phosphine
  • the amount of catalyst used is at least 1% to an excess based on the starting material (VIII).
  • the reaction is usually carried out at temperatures of 20 °C - 160 °C and preferably at 20 °C - 120 °C.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • reaction is generally carried out under atmospheric pressure but it is also possible to operate under elevated pressure.
  • the compounds (Iz) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography.
  • Compounds of formula (VIII) can be prepared using the general method as described in scheme 7. It can alternatively be generated from the compound of the general formula (Villa) where R 1 is hydrogen, namely by alkylation as described in scheme 13. Compounds of formula (Villa) can be prepared from the compound of the general formula (X) by halogenation.
  • Compounds of formula (IXb) can be generated from the compound of the general formula (XIX) where R 2d is C C 6 -alkyl, C 3 -C 6 -cycloalkyl, heterocyclyl, C 2 -C 6 -alkenyl, C r C 6 -alkylC(0)OCi-C 6 - alkyl, C r C 6 -alkyl-OC(0)Ci-C 6 -alkyl, tri(C r C 6 -alkyl)silyl, C 6 -Ci 4 -aryl, C 6 -Ci 4 -heteroaryl, each of which optionally mono- or polysubstituted by identical or different substituents from the group consisting of halogen, cyano, Ci-C6-alkyl, Ci-C6-alkylamino, Ci-C6-dialkylamino , NH 2 , heterocyclyl, C(0)OCi-C 6 -alkyl, OC
  • the alkynone (XIX) can be prepared by treating acid chloride (XX) with an alkyne for example by transition-metal catalysis e.g. as described in Tetrahedron Lett. 2006, 47, 5527-5530 or in
  • the alkynone (XIX) can be prepared by carbonylative C-C coupling using thiophene halides (XIII) with an alkyne employing carbon monoxide as described e.g. in Synlett 2008, 6, 886-888 or J. Org. Chem. 2005, 70, 6097-6100.
  • Compounds of general formula (XII) (where B a is a boron derivative) are commercially available or can be prepared as described in scheme 11.
  • a method for preparing (XII) is the reaction of Halogenoheterocycles of general formula (VI) with bispinacolatodiboron in the presence of a catalyst (e.g. palladium acetate) and a ligand (e.g. diphenylphosphinoferrocene), a base (e.g. potassium acetate) and a solvent (e.g. dimethyl sulfoxide) according to literature procedure (Bioorg. Med Chem. Lett. 2006, 16, 5, 1277-1281, and WO 04/014913).
  • a catalyst e.g. palladium acetate
  • a ligand e.g. diphenylphosphinoferrocene
  • a base e.g. potassium acetate
  • solvent e.g. dimethyl sulfoxide
  • Suitable solvents for carrying out this reaction are customary inert organic solvents, such as for example Sulfoxides (e.g. dimethylsulfoxide), cyclic ethers (e.g. Dioxane) and amides (e.g. N,N- dimethylformamide).
  • Sulfoxides e.g. dimethylsulfoxide
  • cyclic ethers e.g. Dioxane
  • amides e.g. N,N- dimethylformamide
  • the reaction can also be carried out in mixtures of two or more of these solvents.
  • the preferred solvents are dimethyl sulfoxide and dioxane.
  • the reaction is usually carried out at temperatures between 80 ° C and 120 ° C, the preferred reaction temperature is 85 ° C - 90 ° C.
  • the reaction time varies depending on the scale and temperature of the reaction, but is generally between one hour and 16 hours.
  • compounds of general formula (XII) can be prepared by metalation of the haloheterocycle (VI) with a b as e (e.g. n-butyllithium) in a solvent (e.g. diethyl ether or tetrahydrofurane) and subsequent reaction with a trialkylborate (e.g. B(Oi-Pr) 3 or B(OMe)s) according to known literature methods (Synthesis 2004, 4, 469-483, and references described therein).
  • a b as e e.g. n-butyllithium
  • a solvent e.g. diethyl ether or tetrahydrofurane
  • a trialkylborate e.g. B(Oi-Pr) 3 or B(OMe)s
  • At least one equivalent of base e.g. butyl lithium or isopropylmagnesium chloride
  • the reaction is usually carried out at temperatures of -80 °C - 20 °C depending on the base used to perform the reaction. During the reaction a change in temperature may be beneficial or necessary to ensure the reaction with the second reactant.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the compounds (XII) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography, or they can, if appropriate, also be used for the next step without prior purification.
  • a method for preparing compounds of general formula (XII) is the reaction of Haloheterocyclen of general formula (VI) with Hexaalkylditin (e.g. 1,1,1,2,2,2-Hexabutylditin) in the presence of a catalyst (e.g. dichlorobis(triphenylphoshine)palladium), when appropriate with a fluoride ion source in a solvent (e.g. tetrahydrofuran or diethyl ether) according to literature methods (WO 03/095455 or WO 07/104538).
  • a catalyst e.g. dichlorobis(triphenylphoshine)palladium
  • compounds of general formula (XII) can be prepared by metalation of the haloheterocycle (VI) with a b as e (e.g. n-butyllithium) in a solvent (e.g. diethyl ether or tetrahydrofurane) and subsequent reaction with a trialkyltin chloride (e.g. tributyltin chloride) according to known literature methods (WO 08/08747 and Tetrahedron 1994, 275-284).
  • a b as e e.g. n-butyllithium
  • solvent e.g. diethyl ether or tetrahydrofurane
  • a trialkyltin chloride e.g. tributyltin chloride
  • At least one equivalent of base e.g. butyl lithium or isopropylmagnesium chloride is employed, based on the starting material of the general formula (VI).
  • the reaction is usually carried out at temperatures of -80 °C - 20 °C depending on the base used to perform the reaction. During the reaction a change in temperature may be beneficial or necessary to ensure the reaction with the second reactant.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the compounds (XII) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography, or they can, if appropriate, also be used for the next step without prior purification.
  • Process H v) Compound of general formula (I) are prepared according to scheme 8 via alkylation or acylation of a compound of general formula (lb) using the same procedures as describe for process B, step d) in scheme 3.
  • w) Compounds of formula (lb) may be obtained by deprotection of compounds of formula (Io) under stated of the art methods depending on the nature of the protective group.
  • tetrahydropyranyl as protective group can be deprotected under acidic condition. It is to be noted that weak deprotecting group may be deprotected during the course of the reaction.
  • Compounds of general formula (Io) can be for prepared by coupling the pyrazoles of general formula (XIV) (where B represents a boronic ester or boronic acid) with compounds of formula (XIII) (where Z 4 is a leaving group such as chlorine, iodine, bromine or triflate) in the presence of a catalyst, a base, a ligand and a suitable solvent at an appropriate temperature according to known literature procedures (Top Curr. Chem 2002, 219, 1 1 ; A. Suzuki, Org. Chem 1999, 28, 147 and literature cited therein, Org Lett. 2005, 7, 21, 4753-4756).
  • Compounds of general formula (Io) can alternatively be prepared by coupling the pyrazoles of general formula (XIV) (where B represents for trialkyltin) with compounds of formula (XIII) (where Z4 is a leaving group such as chlorine, bromine) in the presence of a catalyst, an inorganic or organic halide salt if appropriate, optionally a ligand and a suitable solvent at an appropriate temperature according to known literature procedures (Synthesis 1992, 803-815).
  • Suitable catalyst for carrying out the above mentioned processes according to the invention may be chosen as being a metal salt or complex.
  • Suitable metal derivatives for this purpose are based on palladium.
  • Suitable metal salts or complexes for this purpose are palladium chloride, palladium acetate, tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium dichloride or 1 , 1 '-bis(diphenylphosphino) ferrocenepalladium(II) chloride.
  • a palladium complex in the reaction mixture by separate addition to the reaction of a palladium salt and a ligand or salt, such as a phosphine, for example triethylpho sphine, tri-tert-butylphosphine, tricyclohexylphosphine, 2-(dicyclohexyl- phosphine)biphenyl, 2-(di-tert-butylphosphin)biphenyl, 2-(dicyclohexylphosphine)-2'-(N,N- dimethylamino)-biphenyl, triphenylphosphine, tris-(o-tolyl)pho sphine, so dium 3-(diphe- nylphosphino)benzolsulfonate, tris-2-(methoxyphenyl)phosphine, 2,2'-bis-(diphenylphosphine)- 1 , 1 '
  • the amount of catalyst used is at least 1% to an excess based on the starting material (XIII).
  • the reaction is usually carried out at temperatures of 20 °C - 160 °C and preferably at 20 °C - 120 °C.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the reaction is generally carried out under atmospheric pressure but it is also possible to operate under elevated pressure.
  • the compounds (Io) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography, or they can, if appropriate, also be used for the next step without prior purification.
  • Compounds of general formula (XIII) are commercially available or can be prepared using known organic synthesis techniques like for example via metallation (as described in Chem. A Eur. J., 2009, 1 5, 5 176) or via halogenation with an halogenating agent like for example N- bromosuccinimide (as described in WO 07/143597).
  • the reaction is usually carried out at temperatures of -80 °C - 20 °C depending on the base used to perform the reaction. During the reaction a change in temperature may be beneficial or necessary to ensure the reaction with the second reactant.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the compounds (XIV) are removed from the reaction mixture using one of the customary separation techniques. If required, the compounds are purified by recrystallisation, distillation or chromatography, or they can, if appropriate, also be used for the next step without prior purification.
  • compounds of general formula (XIV) where B b is a tin derivative can be prepared by metalation of the protected pyrazole (XV) with a base (e.g. n-butyllithium) in a solvent (e.g. diethyl ether or tetrahydrofurane) and subsequent reaction with a trialkyltin chloride (e.g. tributyltin chloride) according to known literature methods (WO 06/108591).
  • a base e.g. n-butyllithium
  • solvent e.g. diethyl ether or tetrahydrofurane
  • a trialkyltin chloride e.g. tributyltin chloride
  • At least one equivalent of base e.g. butyl lithium or isopropylmagnesium chloride
  • base e.g. butyl lithium or isopropylmagnesium chloride
  • the reaction is usually carried out at temperatures of -80 °C - 20 °C depending on the base used to perform the reaction. During the reaction a change in temperature may be beneficial or necessary to ensure the reaction with the second reactant.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • Compounds of general formula (XV) can be prepared for example by coupling the bromopyrazole (XVI) with metallated heterocycles of general formula (XII) (where M represents a boronic ester such as pinacol borane or a boronic acid) in the presence of a catalyst, a base and a ligand if appropriate and a suitable solvent at an appropriate temperature according to known literature procedures produce (Top Curr. Chem 2002, 219, 11; Org Lett. 2005, 7, 21, 4753-4756; Org. Chem 1999, 28, 147 and the literature cited therein).
  • Compounds of the formula (XV) can also be prepared by coupling the bromopyrazole (XVI) with metallated heterocycles of general formula (XII) where M represents trialkyltin (e.g. tributyltin).
  • the reaction can be performed in the presence of a catalyst, and a ligand if appropriate and a suitable solvent at an appropriate temperature according to known literature procedures produce (Synthesis 1992, 803-815).
  • Suitable catalyst for carrying out the above mentioned processes according to the invention may be chosen as being a metal salt or complex.
  • Suitable metal derivatives for this purpose are based on palladium.
  • Suitable metal salts or complexes for this purpose are palladium chloride, palladium acetate, tetrakis(triphenylphosphine)palladium, bis(triphenylphosphine)palladium dichloride or 1 , 1 '-bis(diphenylphosphino) ferrocenepalladium(II) chloride.
  • a palladium complex in the reaction mixture by separate addition to the reaction of a palladium salt and a ligand or salt, such as a phosphine, for example triethylpho sphine, tri-tert-butylphosphine, tricyclohexylphosphine, 2-(dicyclohexyl- phosphine)biphenyl, 2-(di-tert-butylphosphin)biphenyl, 2-(dicyclohexylphosphine)-2'-(N,N- dimethylamino)-biphenyl, triphenylphosphine, tris-(o-tolyl)phosphine, sodium 3-(diphenylphos- phino)benzolsulfonate, tris-2-(methoxyphenyl)phosphine, 2,2'-bis-(diphenylphosphine)-l,l'- binaphth
  • the amount of catalyst used is at least 1% to an excess based on the starting material (XVI).
  • the reaction is usually carried out at temperatures of 20 °C - 160 °C and preferably at 20 °C - 120 °C.
  • the reaction time varies depending on the scale of the reaction and the reaction temperature, but is generally between a couple of minutes and 48 hours.
  • the reaction is generally carried out under atmospheric pressure but it is also possible to operate under elevated pressure.
  • the intermediate of formula (XVII) can be synthesized by halogenation of a compound of formula (XVIII) using a suitable halogenating agent such as N-bromosuccinimide, bromine or the like in an appropriate solvent such as dimethylformamide, acetic acid, mixtures thereof or the like.
  • a suitable halogenating agent such as N-bromosuccinimide, bromine or the like in an appropriate solvent such as dimethylformamide, acetic acid, mixtures thereof or the like.
  • the invention furthermore provides the non-medicinal use of the heterocyclyl-substituted thiazoles according to the invention for controlling unwanted microorganisms.
  • the invention furthermore relates to a composition for controlling unwanted microorganisms which comprises at least one heterocyclyl-substituted thiazole according to the present invention.
  • the invention relates to a method for controlling unwanted microorganisms, characterized in that the heterocyclyl-substituted thiazoles according to the invention are applied to the microorganisms and/or in their habitat.
  • the invention furthermore relates to a seed treated with at least one heterocyclyl-substituted thiazole according to the invention.
  • a last subject-matter of the invention relates to a method for protecting seed against unwanted microorganisms by using seed treated with at least one heterocyclyl-substituted thiazole according to the present invention.
  • the compounds according to the invention have strong microbicidal action and can be used for controlling unwanted microorganisms, such as fungi and bacteria, in crop protection and in the protection of materials.
  • heterocyclyl-substituted thiazoles of the formula (I) according to the invention have very good fungicidal properties and can be used in crop protection, for example, for controlling Plasmodio- phoromycetes, Oomycetes, Chytridiomycetes, Zygomycetes, Ascomycetes, Basidiomycetes and Deuteromycetes.
  • bactericides can be used for controlling, for example, Pseudomonadaceae, Rhizobiaceae, Enterobacteriaceae, Corynebacteriaceae and Streptomycetaceae.
  • the fungicidal compositions according to the invention can be used for the curative or protective control of phytopathogenic fungi. Accordingly, the invention also relates to curative and protective methods for controlling phytopathogenic fungi using the active compounds or compositions according to the invention, which are applied to the seed, the plant or plant parts, the fruit or the soil in which the plants grow.
  • compositions according to the invention for controlling phytopathogenic fungi in crop protection comprise an effective, but non-phytotoxic amount of the active compounds according to the invention.
  • Effective, but non-phytotoxic amount means an amount of the composition according to the invention which is sufficient to control the fungal disease of the plant in a satisfactory manner or to eradicate the fungal disease completely, and which, at the same time, does not cause any significant symptoms of phytotoxicity.
  • this application rate may vary within a relatively wide range. It depends on a plurality of factors, for example on the fungus to be controlled, the plant, the climatic conditions and the ingredients of the compositions according to the invention.
  • Plants are to be understood here as meaning all plants and plant populations, such as wanted and unwanted wild plants or crop plants (including naturally occurring crop plants).
  • Crop plants can be plants which can be obtained by conventional breeding and optimization methods or by biotechnological and genetic engineering methods or combinations of these methods, including the transgenic plants and including plant cultivars which can or cannot be protected by varietal property rights.
  • Parts of plants are to be understood as meaning all above-ground and below-ground parts and organs of the plants, such as shoot, leaf, flower and root, examples which may be mentioned being leaves, needles, stems, trunks, flowers, fruit bodies, fruits and seeds and also roots, tubers and rhizomes.
  • Plant parts also include harvested material and vegetative and generative propagation material, for example seedlings, tubers, rhizomes, cuttings and seeds.
  • plants which can be treated according to the invention cotton, flax, grapevines, fruit, vegetables, such as Rosaceae sp. (for example pomaceous fruit, such as apples and pears, but also stone fruit, such as apricots, cherries, almonds and peaches and soft fruit such as strawberries), Ribesioidae sp., Juglandaceae sp., Betulaceae sp., Anacardiaceae sp., Fagaceae sp., Moraceae sp., Oleaceae sp., Actinidaceae sp., Lauraceae sp., Musaceae sp.
  • Rosaceae sp. for example pomaceous fruit, such as apples and pears, but also stone fruit, such as apricots, cherries, almonds and peaches and soft fruit such as strawberries
  • Rosaceae sp. for example pomaceous fruit, such as apples and pears, but also stone fruit,
  • Rubiaceae sp. for example coffee
  • Theaceae sp. Sterculiceae sp.
  • Rutaceae sp. for example lemons, oranges and grapefruit
  • Solanaceae sp. for example tomatoes
  • Liliaceae sp. Asteraceae sp.
  • Umbelliferae sp. for example Cruciferae sp.
  • Chenopodiaceae sp. Cucurbitaceae sp. (for example cucumbers), Alliaceae sp. (for example leek, onions), Papilionaceae sp.
  • Gramineae sp. for example maize, lawn, cereals such as wheat, rye, rice, barley, oats, millet and triticale
  • Asteraceae sp. for example sunflowers
  • Brassicaceae sp. for example white cabbage, red cabbage, broccoli, cauliflowers, brussels sprouts, pak choi, kohlrabi, garden radish, and also oilseed rape, mustard, horseradish and cress
  • Fabacae sp. for example beans, peanuts
  • Papilionaceae sp. for example soya beans
  • cereal plants are treated according to the invention.
  • Some pathogens of fungal diseases which can be treated according to the invention may be mentioned by way of example, but not by way of limitation:
  • Blumeria species such as, for example, Blumeria graminis
  • Podosphaera species such as, for example, Podosphaera leuco- tricha
  • Sphaerotheca species such as, for example, Sphaerotheca fuliginea
  • Uncinula species such as, for example, Uncinula necator
  • Gymnosporangium species such as, for example, Gymnosporangium sabinae
  • Hemileia species such as, for example, Hemileia vastatrix
  • Phakopsora species such as, for example, Phakopsora pachyrhizi and Phakopsora meibomiae
  • Puccinia species such as, for example, Puccinia recondita, Puccinia graminis or Puccinia striformis
  • Uromyces species such as, for example, Uromyces appendiculatus
  • Albugo species such as, for example, Albugo cundida
  • Bremia species such as, for example, Bremia lactucae
  • Peronospora species such as, for example, Peronospora pisi or P.
  • Phytophthora species such as, for example Phytophthora infestans
  • Plasmopara species such as, for example, Plasmopara viticola
  • Pseudoperonospora species such as, for example, Pseudoperonospora humuli or Pseudoperonospora cubensis
  • Pythium species such as, for example, Pythium ultimum
  • Ear and panicle diseases caused, for example, by Alternaria species, such as, for example, Alternaria spp.; Aspergillus species, such as, for example, Aspergillus flavus; Cladosporium species, such as, for example, Cladosporium cladosporioides; Claviceps species, such as, for example, Claviceps purpurea; Fusarium species, such as, for example, Fusarium culmorum; Gibberella species, such as, for example, Gibberella zeae; Monographella species, such as, for example, Monographella nivalis; Stagonospora species, such as for example, Stagonospora nodorum;
  • Sphacelotheca species such as, for example, Sphacelotheca reiliana
  • Tilletia species such as, for example, Tilletia caries or Tilletia controversa
  • Urocystis species such as, for example, Urocystis occulta
  • Ustilago species such as, for example, Ustilago nuda
  • Botrytis species such as, for example, Botrytis cinerea
  • Penicillium species such as, for example, Penicillium expansum or Penicillium purpurogenum
  • Rhizopus species such as, for example, Rhizopus stolonifer
  • Sclerotinia species such as, for example, Sclerotinia sclerotiorum
  • Verticilium species such as, for example, Verticilium species, such as, for example, Verticilium species,
  • Nectria species such as, for example, Nectria galligena
  • Exobasidium species such as, for example, Exobasidium vexams
  • Taphrina species such as, for example, Taphrina deformans
  • Degenerative diseases of woody plants caused, for example, by Esca species such as, for example, Phaeomoniella chlamydospora, Phaeoacremonium aleophilum or Fomitiporia mediterranea
  • Ganoderma species such as, for example, Ganoderma boninense;
  • Botrytis species such as, for example, Botrytis cinerea
  • Diseases of plant tubers caused, for example, by Rhizoctonia species, such as, for example, Rhizoctonia solani
  • Helminthosporium species such as, for example, Helminthosporium solani
  • Xanthomonas species such as, for example, Xanthomonas campestris pv. oryzae
  • Pseudomonas species such as, for example, Pseudomonas syringae pv. lachrymans
  • Erwinia species such as, for example, Erwinia amylovora.
  • phytophthora rot (Phytophthora megasperma), brown stem rot (Phialophora gregata), pythium rot (Pythium aphanidermatum, Pythium irregulare, Pythium debaryanum, Pythium myriotylum, Pythium ultimum), rhizoctonia root rot, stem decay, and damping-off (Rhizoctonia solani), sclerotinia stem decay (Sclerotinia sclerotiorum), sclerotinia southern blight (Sclerotinia rolfsii), thielaviopsis root rot (Thielaviopsis basicola).
  • the active compounds according to the invention also show a strong invigorating action in plants. Accordingly, they are suitable for mobilizing the internal defenses of the plant against attack by unwanted microorganisms.
  • plant-invigorating (resistance-inducing) substances are to be understood as meaning substances which are capable of stimulating the defence system of plants such that, when the treated plants are subsequently inoculated with unwanted microorganisms, they display substantial resistance to these microorganisms.
  • undesired microorganisms are understood as meaning phytopathogenic fungi and bacteria.
  • the substances according to the invention can be employed for protecting plants against attack by the abovementioned pathogens within a certain period of time after the treatment.
  • the period of time within which their protection is effected is generally extended from 1 to 10 days, preferably 1 to 7 days, after the plants have been treated with the active compounds.
  • the active compounds according to the invention can be employed particularly successfully for controlling diseases in viticulture and in the cultivation of fruit, potatoes and vegetables, such as, for example, in particular against powdery mildew fungi, Oomycetes, such as, for example, Phytophthora, Plasmopara, Pseudoperonospora and Pythium species.
  • the active compounds according to the invention are also suitable for increasing the yield. Moreover, they display a low degree of toxicity and are well tolerated by plants.
  • the compounds according to the invention can, at certain concentrations or application rates, also be used as herbicides, safeners, growth regulators or agents to improve plant properties, or as microbicides, for example as fungicides, antimycotics, bactericides, viricides (including agents against viroids) or as agents against MLO (Mycoplasma-like organisms) and RLO (Rickettsia- like organisms). If appropriate, they can also be employed as insecticides. If appropriate, they can also be employed as intermediates or precursors for the synthesis of other active compounds.
  • the active compounds according to the invention in combination with good plant tolerance and favourable toxicity to warm-blooded animals and being tolerated well by the environment, are suitable for protecting plants and plant organs, for increasing harvest yields and for improving the quality of harvested material in agriculture, in horticulture, in animal husbandry, in forests, in gardens and leisure facilities, in the protection of stored products and of materials, and in the hygiene sector. They are preferably employed as crop protection agents. They are active against normally sensitive and resistant species and against all or some stages of development.
  • the treatment according to the invention of the plants and plant parts with the active compounds or compositions is carried out directly or by action on their surroundings, habitat or storage space using customary treatment methods, for example by dipping, spraying, atomizing, irrigating, evaporating, dusting, fogging, broadcasting, foaming, painting, spreading-on, watering (drenching), drip irrigating and, in the case of propagation material, in particular in the case of seeds, furthermore as a powder for dry seed treatment, a solution for wet seed treatment, a water-soluble powder for slurry treatment, by encrusting, by coating with one or more coats, etc. It is furthermore possible to apply the active compounds by the ultra-low- volume method or to inject the active compound preparation or the active compound itself into the soil.
  • compositions or active compounds according to the invention can furthermore be employed for protecting industrial materials against attack and destruction by unwanted microorganisms, such as, for example, fungi.
  • industrial materials are understood as meaning nonliving materials which have been made for use in technology.
  • industrial materials which are to be protected by active compounds according to the invention from microbial modification or destruction can be glues, sizes, paper and board, textiles, leather, timber, paints and plastic articles, cooling lubricants and other materials which are capable of being attacked or destroyed by microorganisms.
  • Parts of production plants, for example cooling-water circuits, which can be adversely affected by the multiplication of microorganisms may also be mentioned within the materials to be protected.
  • Industrial materials which may be mentioned with preference for the purposes of the present invention are glues, sizes, paper and board, leather, timber, paints, cooling lubricants and heat- transfer fluids, especially preferably timber.
  • compositions or active compounds according to the invention can prevent disadvantageous effects such as rotting, decay, discoloration, decoloration or the formation of mould.
  • the method according to the invention for controlling unwanted fungi can also be employed for protecting storage goods.
  • storage goods are to be understood as meaning natural substances of vegetable or animal origin or process products thereof of natural origin, for which long-term protection is desired.
  • Storage goods of vegetable origin such as, for example, plants or plant parts, such as stems, leaves, tubers, seeds, fruits, grains, can be protected freshly harvested or after processing by (pre)drying, moistening, comminuting, grinding, pressing or roasting.
  • Storage goods also include timber, both unprocessed, such as construction timber, electricity poles and barriers, or in the form of finished products, such as furniture.
  • Storage goods of animal origin are, for example, hides, leather, furs and hairs.
  • the active compounds according to the invention can prevent disadvantageous effects, such as rotting, decay, discoloration, decoloration or the formation of mould.
  • Microorganisms capable of degrading or changing the industrial materials are, for example, bacteria, fungi, yeasts, algae and slime organisms.
  • the active compounds according to the invention preferably act against fungi, in particular moulds, wood-discoloring and wood-destroying fungi (Basidiomycetes) and against slime organisms and algae.
  • Microorganisms of the following genera may be mentioned as examples: Alternaria, such as Alternaria tenuis; Aspergillus, such as Aspergillus niger; Chaetomium, such as Chaetomium globosum; Coniophora, such as Coniophora puetana; Lentinus, such as Lentinus tigrinus; Penicillium, such as Penicillium glaucum; Polyporus, such as Polyporus versicolor; Aureobasidium, such as Aureobasidium pullulans; Sclerophoma, such as Sclerophoma pityophila; Trichoderma, such as Trichoderma viride; Escherichia, such as Escherichia coli; Pseudomonas, such as Pseudomonas aeruginosa; Staphylococcus, such as Staphylococcus aureus.
  • Alternaria such as Alternaria tenuis
  • the present invention furthermore relates to a composition for controlling unwanted microorganisms comprising at least one of the heteracyclyl-substituted thiazoles according to the invention.
  • a composition for controlling unwanted microorganisms comprising at least one of the heteracyclyl-substituted thiazoles according to the invention.
  • These are preferably fungicidal compositions comprising auxiliaries, solvents, carriers, surfactants or extenders suitable for use in agriculture.
  • a carrier is a natural or synthetic, organic or inorganic substance with which the active compounds are mixed or bonded for better applicability, in particular for application to plants or parts of plants or seed.
  • the carrier which may be solid or liquid, is generally inert and should be suitable for use in agriculture.
  • Suitable solid carriers are: for example ammonium salts and ground natural minerals, such as kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, and ground synthetic minerals, such as finely divided silica, alumina and silicates; suitable solid carriers for granules are: for example crushed and fractionated natural rocks, such as calcite, marble, pumice, sepiolite and dolomite, and also synthetic granules of inorganic and organic meals, and granules of organic material, such as paper, sawdust, coconut shells, maize cobs and tobacco stalks; suitable emulsifiers and/or foam-formers are: for example nonionic and anionic emulsifiers, such as polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, for example alkylaryl polyglycol ethers, alkylsulphonates, alkyl sulphates, arylsul
  • oligo- or polymers for example those derived from vinylic monomers, from acrylic acid, from EO and/or PO alone or in combination with, for example, (poly)alcohols or (poly)amines. It is also possible to employ lignin and its sulphonic acid derivatives, unmodified and modified celluloses, aromatic and/or aliphatic sulphonic acids and their adducts with formaldehyde.
  • the active compounds can be converted to the customary formulations, such as solutions, emulsions, wettable powders, water- and oil-based suspensions, powders, dusts, pastes, soluble powders, soluble granules, granules for broadcasting, suspension-emulsion concentrates, natural materials impregnated with active compound, synthetic materials impregnated with active compound, fertilizers and also microencapsulations in polymeric substances.
  • customary formulations such as solutions, emulsions, wettable powders, water- and oil-based suspensions, powders, dusts, pastes, soluble powders, soluble granules, granules for broadcasting, suspension-emulsion concentrates, natural materials impregnated with active compound, synthetic materials impregnated with active compound, fertilizers and also microencapsulations in polymeric substances.
  • the active compounds can be used as such, in the form of their formulations or the use forms prepared therefrom, such as ready-to-use solutions, emulsions, water- or oil-based suspensions, powders, wettable powders, pastes, soluble powders, dusts, soluble granules, granules for broadcasting, suspension-emulsion concentrates, natural materials impregnated with active compound, synthetic materials impregnated with active compound, fertilizers and also microencapsulations in polymeric substances.
  • Application is carried out in a customary manner, for example by pouring, spraying, atomizing, broadcasting, dusting, foaming, painting-on, etc. It is furthermore possible to apply the active compounds by the ultra-low- volume method or to inject the preparation of active compound or the active compound itself into the soil. It is also possible to treat the seed of the plants.
  • the formulations mentioned can be prepared in a manner known per se, for example by mixing the active compounds with at least one customary extender, solvent or diluent, emulsifier, dispersant and/or binder or fixative, wetting agent, water repellant, if appropriate siccatives and UV stabilizers and if appropriate colorants and pigments, antifoams, preservatives, secondary thickeners, glues, gibberellins and other processing auxiliaries.
  • compositions according to the invention include not only formulations which are already ready to use and can be applied to the plant or the seed using a suitable apparatus, but also commercial concentrates which have to be diluted with water prior to use.
  • the active compounds according to the invention can be present as such or in their (commercial) formulations and also in the use forms prepared from these formulations as a mixture with other (known) active compounds, such as insecticides, attractants, sterilants, bactericides, acaricides, nematicides, fungicides, growth regulators, herbicides, fertilizers, safeners and/or semiochemicals.
  • active compounds such as insecticides, attractants, sterilants, bactericides, acaricides, nematicides, fungicides, growth regulators, herbicides, fertilizers, safeners and/or semiochemicals.
  • auxiliaries are substances which are suitable for imparting to the composition itself and/or to preparations derived therefrom (for example spray liquors, seed dressings) particular properties such as certain technical properties and/or also particular biological properties.
  • suitable auxiliaries are: extenders, solvents and carriers.
  • Suitable extenders are, for example, water, polar and nonpolar organic chemical liquids, for example from the classes of the aromatic and non-aromatic hydrocarbons (such as paraffins, alkylbenzenes, alkylnaphthalenes, chlorobenzenes), the alcohols and polyols (which, if appropriate, may also be substituted, etherified and/or esterified), the ketones (such as acetone, cyclohexanone), esters (including fats and oils) and (poly)ethers, the unsubstituted and substituted amines, amides, lactams (such as N-alkylpyrrolidones) and lactones, the sulphones and sulphoxides (such as dimethyl sulphoxide).
  • aromatic and non-aromatic hydrocarbons such as paraffins, alkylbenzenes, alkylnaphthalenes, chlorobenzenes
  • the alcohols and polyols
  • Liquefied gaseous extenders or carriers are liquids which are gaseous at ambient temperature and under atmospheric pressure, for example aerosol propellants, such as halogenated hydrocarbons, and also butane, propane, nitrogen and carbon dioxide.
  • Tackifiers such as carboxymethylcellulose and natural and synthetic polymers in the form of powders, granules and latices, such as gum arabic, polyvinyl alcohol, polyvinyl acetate, or else natural phospholipids, such as cephalins and lecithins and synthetic phospholipids can be used in the formulations.
  • Other possible additives are mineral and vegetable oils.
  • Suitable liquid solvents are essentially: aromatic compounds, such as xylene, toluene or alkylnaphthalenes, chlorinated aromatic compounds or chlorinated aliphatic hydrocarbons, such as chlorobenzenes, chloroethylenes or methylene chloride, aliphatic hydrocarbons, such as cyclohexane or paraffins, for example mineral oil fractions, alcohols, such as butanol or glycol, and also ethers and esters thereof, ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, strongly polar solvents, such as dimethylformamide and dimethyl sulphoxide, and also water.
  • aromatic compounds such as xylene, toluene or alkylnaphthalenes
  • chlorinated aromatic compounds or chlorinated aliphatic hydrocarbons such as chlorobenzenes, chloroethylenes or methylene chloride
  • compositions according to the invention may additionally comprise further components, such as, for example, surfactants.
  • surfactants are emulsifiers and/or foam-formers, dispersants or wetting agents having ionic or nonionic properties, or mixtures of these surfactants.
  • salts of polyacrylic acid salts of lignosulphonic acid, salts of phenolsulphonic acid or naphthalenesulphonic acid, polycondensates of ethylene oxide with fatty alcohols or with fatty acids or with fatty amines, substituted phenols (preferably alkylphenols or arylphenols), salts of sulphosuccinic esters, taurine derivatives (preferably alkyl taurates), phosphoric esters of polyethoxylated alcohols or phenols, fatty esters of polyols, and derivatives of the compounds containing sulphates, sulphonates and phosphates, for example alkylaryl polyglycol ethers, alkylsulphonates, alkyl sulphates, arylsulphonates, protein hydrolysates, lignosulphite waste liquors and methylcellulose.
  • the presence of a surfactant is required if one of the active compounds and/or one of the inert carriers is insoluble in water and the application is carried out in water.
  • the proportion of surfactants is between 5 and 40 per cent by weight of the compositions according to the invention.
  • colorants such as inorganic pigments, for example iron oxide, titanium oxide, Prussian blue, and organic dyes, such as alizarin dyes, azo dyes and metal phthalocyanine dyes, and trace nutrients, such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc.
  • organic dyes such as alizarin dyes, azo dyes and metal phthalocyanine dyes
  • trace nutrients such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc.
  • trace nutrients such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc.
  • Stabilizers such as low-temperature stabilizers, preservatives, antioxidants, light stabilizers or other agents which improve chemical and/or physical stability may also be present. If appropriate, it is also possible for other additional components to be present, for example protective colloids, binders, glues, thickeners, thixotropic agents, penetrants, stabilizers, sequestrants, complex fomers.
  • the active compounds can be combined with any solid or liquid additive customarily used for formulation purposes.
  • the formulations generally comprise between 0.05 and 99% by weight, 0.01 and 98% by weight, preferably between 0.1 and 95% by weight, particularly preferably between 0.5 and 90% by weight, of active compound, very particularly preferably between 10 and 70 per cent by weight.
  • the formulations described above can be employed in a method according to the invention for controlling unwanted microorganisms where the heterocyclyl-substituted thiazoles according to the invention are applied to the microorganisms and/or their habitat.
  • the active compounds according to the invention can also be used in a mixture with known fungicides, bactericides, acaricides, nematicides or insecticides, for example to broaden the activity spectrum or to prevent the development of resistance.
  • Suitable mixing partners are, for example, known fungicides, insecticides, acaricides, nematicides or else bactericides (see also Pesticide Manual, 13th ed.).
  • a mixture with other known active compounds, such as herbicides, or with fertilizers and growth regulators, safeners and/or semiochemicals is also possible.
  • Application is carried out in a manner adapted to the use forms.
  • the invention furthermore comprises a method for treating seed.
  • a further aspect of the present invention relates in particular to seed treated with at least one of the heterocyclyl-substituted thiazoles according to the invention.
  • the seed according to the invention is used in methods for protecting seed agains phytopathogenic harmful fungi.
  • seed treated with at least one active compound according to the invention is used.
  • compositions and active compounds according to the invention are also suitable for treating seed.
  • a large part of the damage to crop plants which is caused by harmful organisms occurs when the seed is attacked during storage or after the seed is introduced into the soil, and also during and after germination of the plant. This phase is particularly critical since the roots and shoots of the growing plant are particularly sensitive and even minor damage can lead to the death of the whole plant. Protecting the seed and the germinating plant by the use of suitable compositions is therefore of great interest.
  • the present invention therefore also relates to a method for the protection of seed and germinating plants from attack by animal pests and/or phytopathogenic harmful fungi, by treating the seed with a composition according to the invention.
  • the invention likewise relates to the use of the compositions according to the invention for the treatment of seed for protecting the seed and the germinating plant from phytopathogenic fungi.
  • the invention relates to seed which has been treated with a composition according to the invention so as to afford protection from phytopathogenic fungi.
  • compositions according to the invention mean that treatment of the seed with these compositions not only protects the seed itself, but also the resulting plants after emergence, from animal pests and/or phytopathogenic harmful fungi. In this manner, the immediate treatment of the crop at the time of sowing or shortly thereafter can be dispensed with.
  • compositions and active compounds according to the invention can be used in particular also for transgenic seed, where the plant growing from this seed is capable of expressing a protein which acts against pests.
  • a seed By treating such a seed with the compositions and active compounds according to the invention, is is possible to control certain pests even by the expression of the, for example, insecticidal protein.
  • a further synergistic effect may be observed here, which further improves the effectiveness of the protection against attack by pests.
  • compositions according to the invention are suitable for protecting seed of any plant variety which is employed in agriculture, in the greenhouse, in forests or in horticulture.
  • this takes the form of seed of cereals (such as wheat, barley, rye, millet and oats), maize, cotton, soya beans, rice, potatoes, sunflowers, beans, coffee, beet (for example sugar beet and fodder beet), peanuts, vegetables (such as tomatoes, cucumbers, onions and lettuce), lawns and ornamental plants.
  • cereals such as wheat, barley, rye, millet and oats
  • maize cotton, soya beans, rice, potatoes, sunflowers, beans, coffee, beet (for example sugar beet and fodder beet)
  • peanuts such as tomatoes, cucumbers, onions and lettuce
  • lawns and ornamental plants such as tomatoes, cucumbers, onions and lettuce
  • transgenic seed With the compositions or active compounds according to the invention is also of particular importance.
  • the heterologous gene in transgenic seed may be derived, for example, from microorganisms of the species Bacillus, Rhizobium, Pseudomonas, Serratia, Trichoderma, Clavibacter, Glomus or Gliocladium.
  • This heterologous gene preferably originates from Bacillus sp., the gene product having activity against the European corn borer and/or the Western corn root worm.
  • the composition according to the invention is applied to the seed either alone or in a suitable formulation.
  • the seed is treated in a state which is stable enough to avoid damage during treatment.
  • the seed may be treated at any point in time between harvest and sowing.
  • the seed usually used has been separated from the plant and freed from cobs, shells, stalks, coats, hairs or the flesh of the fruits.
  • seed which has been harvested, cleaned and dried to a moisture content of below 15% by weight.
  • the amount of the composition according to the invention applied to the seed and/or the amount of further additives is chosen in such a way that the germination of the seed is not adversely affected, or that the resulting plant is not damaged. This must be borne in mind in particular in the case of active compounds which may have phytotoxic effects at certain application rates.
  • compositions according to the invention can be applied directly, that is to say without comprising further components and without having been diluted.
  • suitable formulations and methods for the treatment of seed are known to the skilled worker and are described, for example, in the following documents: US 4,272,417 A, US 4,245,432 A, US 4,808,430 A, US 5,876,739 A, US 2003/0176428 Al, WO 2002/080675 Al, WO 2002/028186 A2.
  • the active compound which can be used according to the invention can be converted into customary seed dressing formulations, such as solutions, emulsions, suspensions, powders, foams, slurries or other coating materials for seed, and also ULV formulations.
  • formulations are prepared in a known manner by mixing the active compounds or active compound combinations with customary additives, such as, for example, customary extenders and also solvents or diluents, colorants, wetting agents, dispersants, emulsifiers, defoamers, preservatives, secondary thickeners, adhesives, gibberellins and also water.
  • customary additives such as, for example, customary extenders and also solvents or diluents, colorants, wetting agents, dispersants, emulsifiers, defoamers, preservatives, secondary thickeners, adhesives, gibberellins and also water.
  • Suitable colorants that may be present in the seed dressing formulations which can be used according to the invention include all colorants customary for such purposes. Use may be made both of pigments, of sparing solubility in water, and of dyes, which are soluble in water. Examples that may be mentioned include the colorants known under the designations rhodamine B, C.I. Pigment Red 112, and C.I. Solvent Red 1.
  • Suitable wetting agents that may be present in the seed dressing formulations which can be used according to the invention include all substances which promote wetting and are customary in the formulation of active agrochemical compounds. With preference it is possible to use alkylnaphthalene- sulphonates, such as diisopropyl- or diisobutylnaphthalene-sulphonates.
  • Suitable dispersants and/or emulsifiers that may be present in the seed dressing formulations which can be used according to the invention include all nonionic, anionic, and cationic dispersants which are customary in the formulation of active agrochemical compounds. With preference, it is possible to use nonionic or anionic dispersants or mixtures of nonionic or anionic dispersants.
  • Particularly suitable nonionic dispersants are ethylene oxide-propylene oxide block polymers, alkylphenol polyglycol ethers, and tristyrylphenol polyglycol ethers, and their phosphated or sulphated derivatives.
  • Particularly suitable anionic dispersants are lignosulphonates, polyacrylic salts, and arylsulphonate- formaldehyde condensates.
  • Suitable defoamers that may be present in the seed dressing formulations which can be used according to the invention include all foam-inhibiting substances which are customary in the formulation of active agrochemical compounds. With preference it is possible to use silicone defoamers and magnesium stearate.
  • Suitable preservatives that may be present in the seed dressing formulations which can be used according to the invention include all substances which can be used for such purposes in agrochemical compositions. By way of example, mention may be made of dichlorophen and benzyl alcohol hemiformal.
  • Suitable secondary thickeners that may be present in the seed dressing formulations which can be used according to the invention include all substances which can be used for such purposes in agrochemical compositions. Preferred suitability is possessed by cellulose derivatives, acrylic acid derivatives, xanthan, modified clays, and finely divided silica.
  • Suitable adhesives that may be present in the seed dressing formulations which can be used according to the invention include all customary binders which can be used in seed dressing. With preference, mention may be made of polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol and tylose.
  • the gibberellins are known (cf. R. Wegler StammChemie der convinced- and Schadlingsbekampfungsstoff", Vol. 2, Springer Verlag, 1970, pp. 401-412).
  • the seed dressing formulations which can be used according to the invention may be used directly or after dilution with water beforehand to treat seed of any of a very wide variety of types.
  • the concentrates or the preparations obtainable therefrom by dilution with water may be used to dress the seed of cereals, such as wheat, barley, rye, oats, and triticale, and also the seed of maize, rice, oilseed rape, peas, field beans, cotton, sunflowers, and beets, or else vegetable seed of any of a very wide variety of kinds.
  • the seed dressing formulations which can be used according to the invention or their dilute preparations may also be used to dress seed of transgenic plants. In this context, additional synergistic effects may also arise in interaction with the substances formed by expression.
  • Suitable mixing equipment for treating seed with the seed dressing formulations which can be used according to the invention or the preparations prepared from them by adding water includes all mixing equipment which can commonly be used for dressing.
  • the specific procedure adopted when dressing comprises introducing the seed into a mixer, adding the particular desired amount of seed dressing formulation, either as it is or following dilution with water beforehand, and carrying out mixing until the formulation is uniformly distributed on the seed.
  • a drying operation follows.
  • the application rate of the seed dressing formulations which can be used according to the invention may be varied within a relatively wide range. It depends on the respective content of the active compounds in the formulations and on the seed. In general, the application rates of active compound combination are between 0.001 and 50 g per kilogram of seed, preferably between 0.01 and 15 g per kilogram of seed.
  • the compounds of the formula (I) according to the invention also have very good antimycotic activity. They have a very broad antimycotic activity spectrum in particular against dermatophytes and yeasts, moulds and diphasic fungi (for example against Candida species such as Candida albicans, Candida glabrata) and Epidermophyton floccosum, Aspergillus species such as Aspergillus niger and Aspergillus fumigatus, Trichophyton species such as Trichophyton mentagrophytes, Microsporon species such as Microsporon canis and audouinii. The enumeration of these fungi does by no means limit the mycotic spectrum which can be covered, but is only for illustration. Accordingly, the active compounds of the formula (I) according to the invention can be used both in medical and in non-medical applications.
  • the active compounds can be applied as such, in the form of their formulations or the use forms prepared therefrom, such as ready-to-use solutions, suspensions, wettable powders, pastes, soluble powders, dusts and granules. Application is carried out in a customary manner, for example by watering, spraying, atomizing, broadcasting, dusting, foaming, painting-on, etc. It is also possible to apply the active compounds by the ultra-low-volume method or to inject the preparation of active compound or the active compound itself into the soil. It is also possible to treat the seed of the plants.
  • the application rates can be varied within a relatively wide range, depending on the type of application.
  • the application rate of the active compounds according to the invention is ⁇ in the treatment of parts of plants, for example leaves: from 0.1 to 10 000 g/ha, preferably from 10 to 1000 g/ha, particularly preferably from 50 to 300 g/ha (when the application is by watering or dripping, it is possible to reduce the application rate even more, in particular when inert substrates such as rock wool or perlite are used);
  • the active compounds according to the invention are applied in the known manner by enteral administration in the form of, for example, tablets, capsules, drinks, drenches, granules, pastes, boluses, the feed-through method, suppositories, by parenteral administration, such as, for example, by injections (intramuscular, subcutaneous, intravenous, intraperitoneal and the like), implants, by nasal application, by dermal application in the form of, for example, bathing or dipping, spraying, pouring-on and spotting-on, washing, dusting, and with the aid of active-compound-comprising shaped articles such as collars, ear tags, tail tags, limb bands, halters, marking devices and the like.
  • enteral administration in the form of, for example, tablets, capsules, drinks, drenches, granules, pastes, boluses, the feed-through method, suppositories
  • parenteral administration such as, for example, by injections (intr
  • the active compounds of the formula (I) can be applied as formulations (for example powders, emulsions, flowables) which comprise the active compounds in an amount of from 1 to 80% by weight, either directly or after 100- to 10 000-fold dilution, or else as a chemical bath.
  • the ready-to-use compositions may comprise further insecticides and, if appropriate, one or more further fungicides.
  • the compounds according to the invention can also be used for protecting objects which come into contact with salt water or brackish water, such as hulls, screens, nets, buildings, moorings and signalling systems, against colonization.
  • the compounds according to the invention can furthermore be employed as antifouling agents.
  • the treatment method according to the invention can be used for treating genetically modified organisms (GMOs), for example plants or seeds.
  • GMOs genetically modified organisms
  • Genetically modified plants (or transgenic plants) are plants in which a heterologous gene has been stably integrated into the genome.
  • heterologous gene essentially means a gene which is provided or assembled outside the plant and when introduced in the nuclear, chloroplastic or mitochondrial genome gives the transformed plant new or improved agronomic or other properties by expressing a protein or polypeptide of interest or by downregulating or silencing other gene(s) which is/are present in the plant (using for example, antisense technology, cosuppression technology or RNA interference (RNAi) technology.
  • RNAi RNA interference
  • a heterologous gene that is located in the genome is also called a transgene.
  • a transgene that is defined by its particular location in the plant genome is called a transformation or transgenic event.
  • the treatment according to the invention may also result in superadditive (“synergistic”) effects.
  • superadditive superadditive
  • the following effects which exceed the effects which were actually to be expected, are possible: reduced application rates and/or a widening of the activity spectrum and/or an increase in the activity of the active compounds and compositions which can be used according to the invention, better plant growth, increased tolerance to high or low temperatures, increased tolerance to drought or to water or soil salt content, increased flowering performance, easier harvesting, accelerated maturation, higher harvest yields, bigger fruits, larger plant height, greener leaf colour, earlier flowering, higher quality and/or a higher nutritional value of the harvested products, higher sugar concentration within the fruits, better storage stability and/or processability of the harvested products.
  • the active compound combinations according to the invention may also have a strengthening effect in plants. Accordingly, they are also suitable for mobilizing the defence system of the plant against attack by unwanted phytopathogenic fungi and/or microorganisms and/or viruses. This may, if appropriate, be one of the reasons for the enhanced activity of the combinations according to the invention, for example against fungi.
  • Plant-strengthening (resistance-inducing) substances are to be understood as meaning, in the present context, those substances or combinations of substances which are capable of stimulating the defence system of plants in such a way that, when subsequently inoculated with unwanted phytopathogenic fungi and/or microorganisms and/or viruses, the treated plants display a substantial degree of resistance to these unwanted phytopathogenic fungi and/or microorganisms and/or viruses.
  • unwanted phytopathogenic fungi and/or microorganisms and/or viruses are to be understood as meaning phytopathogenic fungi, bacteria and viruses.
  • the substances according to the invention can be employed for protecting plants against attack by the abovementioned pathogens within a certain period of time after the treatment.
  • the period of time within which protection is effected generally extends from 1 to 10 days, preferably 1 to 7 days, after the treatment of the plants with the active compounds.
  • Plants and plant cultivars which are preferably treated according to the invention include all plants with genetic material which bestows upon these plants particularly advantageous useful properties (whether this was achieved by breeding and/or biotechnology is immaterial).
  • Plants and plant cultivars which are also preferably treated according to the invention are resistant against one or more biotic stress factors, i.e. said plants have a better defence against animal and microbial pests, such as against nematodes, insects, mites, phytopathogenic fungi, bacteria, viruses and/or viroids.
  • Plants and plant cultivars which may also be treated according to the invention are those plants which are resistant to one or more abiotic stress factors.
  • Abiotic stress conditions may include, for example, drought, cold temperature exposure, heat exposure, osmotic stress, flooding, increased soil salinity, increased mineral exposure, ozone exposure, high light exposure, limited availability of nitrogen nutrients, limited availability of phosphorus nutrients or shade avoidance.
  • Plants and plant cultivars which may also be treated according to the invention are those plants characterized by enhanced yield characteristics.
  • Increased yield in said plants can be the result of, for example, improved plant physiology, growth and development, such as water use efficiency, water retention efficiency, improved nitrogen use, enhanced carbon assimilation, improved photosynthesis, increased germination efficiency and accelerated maturation.
  • Yield can furthermore by affected by improved plant architecture (under stress and non-stress conditions), including early flowering, flowering control for hybrid seed production, seedling vigour, plant size, internode number and distance, root growth, seed size, fruit size, pod size, pod or ear number, seed number per pod or ear, seed mass, enhanced seed filling, reduced seed dispersal, reduced pod dehiscence and lodging resistance.
  • Further yield traits include seed composition, such as carbohydrate content, protein content, oil content and composition, nutritional value, reduction in anti-nutritional compounds, improved processability and better storage stability.
  • Plants that may be treated according to the invention are hybrid plants that already express the characteristic of heterosis or the hybrid effect which results in generally higher yield, vigour, health and resistance towards biotic and abiotic stress factors. Such plants are typically made by crossing an inbred male sterile parent line (the female parent) with another inbred male fertile parent line (the male parent). Hybrid seed is typically harvested from the male sterile plants and sold to growers. Male sterile plants can sometimes (e.g. in corn) be produced by detasseling, (i.e. the mechanical removal of the male reproductive organs or male flowers) but, more typically, male sterility is the result of genetic determinants in the plant genome.
  • male fertility in the hybrid plants which contain the genetic determinants responsible for male sterility, is fully restored.
  • This can be accomplished by ensuring that the male parents have appropriate fertility restorer genes which are capable of restoring the male fertility in hybrid plants that contain the genetic determinants responsible for male sterility.
  • Genetic determinants for male sterility may be located in the cytoplasm. Examples of cytoplasmic male sterility (CMS) were for instance described in Brassica species. However, genetic determinants for male sterility can also be located in the nuclear genome. Male sterile plants can also be obtained by plant biotechnology methods such as genetic engineering.
  • a particularly useful means of obtaining male sterile plants is described in WO 89/10396 in which, for example, a ribonuclease such as a barnase is selectively expressed in the tapetum cells in the stamens. Fertility can then be restored by expression in the tapetum cells of a ribonuclease inhibitor such as barstar.
  • Plants or plant cultivars which may be treated according to the invention are herbicide-tolerant plants, i.e. plants made tolerant to one or more given herbicides. Such plants can be obtained either by genetic transformation, or by selection of plants containing a mutation imparting such herbicide tolerance.
  • Herbicide-tolerant plants are for example glyphosate-tolerant plants, i.e. plants made tolerant to the herbicide glyphosate or salts thereof.
  • glyphosate-tolerant plants can be obtained by transforming the plant with a gene encoding the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS).
  • EPSPS 5-enolpyruvylshikimate-3-phosphate synthase
  • EPSPS genes are the AroA gene (mutant CT7) of the bacterium Salmonella typhimurium, the CP4 gene of the bacterium Agrobacterium sp., the genes encoding a petunia EPSPS, a tomato EPSPS, or an Eleusine EPSPS. It can also be a mutated EPSPS.
  • Glyphosate-tolerant plants can also be obtained by expressing a gene that encodes a glyphosate oxidoreductase enzyme.
  • Glyphosate-tolerant plants can also be obtained by expressing a gene that encodes a glyphosate acetyl transferase enzyme.
  • Glyphosate-tolerant plants can also be obtained by selecting plants containing naturally-occurring mutations of the above-mentioned genes.
  • herbicide-resistant plants are for example plants that are made tolerant to herbicides inhibiting the enzyme glutamine synthase, such as bialaphos, phosphinothricin or glufosinate.
  • Such plants can be obtained by expressing an enzyme detoxifying the herbicide or a mutant glutamine synthase enzyme that is resistant to inhibition.
  • One such efficient detoxifying enzyme is, for example, an enzyme encoding a phosphinothricin acetyltransferase (such as the bar or pat protein from Streptomyces species). Plants expressing an exogenous phosphinothricin acetyltransferase have been described.
  • hydroxyphenylpyruvatedioxygenase HPPD
  • Hydroxyphenylpyruvatedioxygenases are enzymes that catalyse the reaction in which para-hydroxyphenylpyruvate (HPP) is transformed into homogentisate.
  • Plants tolerant to HPPD-inhibitors can be transformed with a gene encoding a naturally-occurring resistant HPPD enzyme, or a gene encoding a mutated HPPD enzyme.
  • Tolerance to HPPD-inhibitors can also be obtained by transforming plants with genes encoding certain enzymes enabling the formation of homogentisate despite the inhibition of the native HPPD enzyme by the HPPD-inhibitor. Tolerance of plants to HPPD inhibitors can also be improved by transforming plants with a gene encoding an enzyme prephenate dehydrogenase in addition to a gene encoding an HPPD-tolerant enzyme.
  • Still further herbicide-resistant plants are plants that are made tolerant to acetolactate synthase (ALS) inhibitors.
  • ALS-inhibitors include, for example, sulphonylurea, imidazolinone, triazolopyrimidines, pyrimidinyloxy(thio)benzoates, and/or sulphonylaminocarbonyltriazolinone herbicides.
  • Different mutations in the ALS enzyme also known as acetohydroxy acid synthase, AHAS
  • AHAS acetohydroxy acid synthase
  • the production of sulphonylurea-tolerant plants and imidazolinone-tolerant plants has been described in the international publication WO 1996/033270. Further sulphonylurea- and imidazolinone-tolerant plants have also been described, for example in WO 2007/024782.
  • plants tolerant to imidazolinone and/or sulphonylurea can be obtained by induced mutagenesis, by selection in cell cultures in the presence of the herbicide or by mutation breeding.
  • Plants or plant cultivars obtained by plant biotechnology methods such as genetic engineering) which may also be treated according to the invention are insect-resistant transgenic plants, i.e. plants made resistant to attack by certain target insects. Such plants can be obtained by genetic transformation, or by selection of plants containing a mutation imparting such insect resistance.
  • insect-resistant transgenic plant includes any plant containing at least one transgene comprising a coding sequence encoding:
  • a crystal protein from Bacillus thuringiensis or a portion thereof which is insecticidal in the presence of a second other crystal protein from Bacillus thuringiensis or a portion thereof, such as the binary toxin made up of the Cy34 and Cy35 crystal proteins; or
  • a hybrid insecticidal protein comprising parts of two different insecticidal crystal proteins from Bacillus thuringiensis, such as a hybrid of the proteins of 1) above or a hybrid of the proteins of 2) above, for example the CrylA.105 protein produced by maize event MON98034 (WO 2007/027777); or
  • VTP3 Aa protein class an insecticidal secreted protein from Bacillus thuringiensis or Bacillus cereus, or an insecticidal portion thereof, such as the vegetative insecticidal proteins (VIP) listed at: http://www.lifesci.sussex.ac.uk/home/Neil_Crickmore/Bt/vip.html, for example proteins from the VTP3 Aa protein class; or
  • a secreted protein from Bacillus thuringiensis or Bacillus cereus which is insecticidal in the presence of a second secreted protein from Bacillus thuringiensis or B. cereus, such as the binary toxin made up of the VIP la and VIP2A proteins; 7) a hybrid insecticidal protein comprising parts from different secreted proteins from Bacillus thuringiensis or Bacillus cereus, such as a hybrid of the proteins in 1 ) above or a hybrid of the proteins in 2) above; or a protein of any one of 1) to 3) above wherein some, particularly 1 to 10, amino acids have been replaced by another amino acid to obtain a higher insecticidal activity to a target insect species, and/or to expand the range of target insect species affected, and/or because of changes induced in the encoding DNA during cloning or transformation (while still encoding an insecticidal protein), such as the VIP3Aa protein in cotton event COT 102.
  • insect-resistant transgenic plants also include any plant comprising a combination of genes encoding the proteins of any one of the above classes 1 to 8.
  • an insect-resistant plant contains more than one transgene encoding a protein of any one of the above classes 1 to 8, to expand the range of target insect species affected or to delay insect resistance development to the plants, by using different proteins insecticidal to the same target insect species but having a different mode of action, such as binding to different receptor binding sites in the insect.
  • Plants or plant cultivars which may also be treated according to the invention are tolerant to abiotic stresses. Such plants can be obtained by genetic transformation, or by selection of plants containing a mutation imparting such stress resistance.
  • Particularly useful stress tolerance plants include: a. plants which contain a transgene capable of reducing the expression and/or the activity of the poly(ADP-ribose)polymerase (PARP) gene in the plant cells or plants. b. plants which contain a stress tolerance-enhancing transgene capable of reducing the expression and/or the activity of the PARG encoding genes of the plants or plant cells; c.
  • PARP poly(ADP-ribose)polymerase
  • plants which contain a stress tolerance-enhancing transgene coding for a plant-functional enzyme of the nicotinamide adenine dinucleotide salvage biosynthesis pathway including nicotinamidase, nicotinate phosphoribosyltransferase, nicotinic acid mononucleotide adenyl transferase, nicotinamide adenine dinucleotide synthetase or nicotinamide phosphoribosyltransferase.
  • Plants or plant cultivars which may also be treated according to the invention show altered quantity, quality and/or storage- stability of the harvested product and/or altered properties of specific ingredients of the harvested product such as, for example: 1) transgenic plants which synthesize a modified starch, which in its physical-chemical characteristics, in particular the amylose content or the amylose/amylopectin ratio, the degree of branching, the average chain length, the side chain distribution, the viscosity behaviour, the gelling strength, the starch grain size and/or the starch grain morphology, is changed in comparison with the synthesized starch in wild type plant cells or plants, so that this modified starch is better suited for special applications.
  • a modified starch which in its physical-chemical characteristics, in particular the amylose content or the amylose/amylopectin ratio, the degree of branching, the average chain length, the side chain distribution, the viscosity behaviour, the gelling strength, the starch grain size and/or the starch grain morphology, is changed in comparison with
  • transgenic plants which synthesize non-starch carbohydrate polymers or which synthesize non-starch carbohydrate polymers with altered properties in comparison to wild type plants without genetic modification.
  • Examples are plants which produce polyfructose, especially of the inulin and levan type, plants which produce alpha- 1,4-glucans, plants which produce alpha- 1,6 branched alpha- 1,4-glucans, and plants producing alternan.
  • Plants or plant cultivars which may also be treated according to the invention are plants, such as cotton plants, with altered fibre characteristics.
  • Such plants can be obtained by genetic transformation, or by selection of plants containing a mutation imparting such altered fibre characteristics and include: a) plants, such as cotton plants, which contain an altered form of cellulose synthase genes, b) plants, such as cotton plants, which contain an altered form of rsw2 or rsw3 homologous nucleic acids; c) plants, such as cotton plants, with an increased expression of sucrose phosphate synthase; d) plants, such as cotton plants, with an increased expression of sucrose synthase; e) plants, such as cotton plants, wherein the timing of the plasmodesmatal gating at the basis of the fibre cell is altered, for example through downregulation of fibre-selective ⁇ -1,3- glucanase; f) plants, such as cotton plants, which have fibres with altered
  • Plants or plant cultivars which may also be treated according to the invention are plants, such as oilseed rape or related Brassica plants, with altered oil profile characteristics.
  • Such plants can be obtained by genetic transformation or by selection of plants containing a mutation imparting such altered oil characteristics and include: a) plants, such as oilseed rape plants, which produce oil having a high oleic acid content; b) plants, such as oilseed rape plants, which produce oil having a low linolenic acid content; c) plants, such as oilseed rape plants, which produce oil having a low level of saturated fatty acids.
  • transgenic plants which comprise one or more genes which encode one or more toxins
  • YIELD GARD® for example maize, cotton, soya beans
  • KnockOut® for example maize
  • BiteGard® for example maize
  • Bt-Xtra® for example maize
  • StarLink® for example maize
  • Bollgard® cotton
  • Nucotn® cotton
  • Nucotn 33B® cotton
  • NatureGard® for example maize
  • Protecta® and NewLeaf® potato
  • herbicide-tolerant plants examples include maize varieties, cotton varieties and soya bean varieties which are sold under the trade names: Roundup Ready® (tolerance to glyphosate, for example maize, cotton, soya beans), Liberty Link® (tolerance to phosphinothricin, for example oilseed rape), IMI® (tolerance to imidazolinone) and SCS® (tolerance to sulphonylurea, for example maize) .
  • Herbicide-resistant plants plants bred in a conventional manner for herbicide tolerance
  • Clearfield® for example maize.
  • transgenic plants which may be treated according to the invention are plants containing transformation events, or a combination of transformation events, that are listed for example in the databases for various national or regional regulatory agencies (see for example http://gmoinfo.jrc.it/gmp_browse.aspx and http://www.agbios.com/dbase.php).
  • the plants listed can be treated particularly advantageously with the compounds of the general formula (I) or the active compound mixtures according to the invention.
  • the preferred ranges indicated above for the active compounds and mixtures also apply to the treatment of these plants. Particular emphasis is given to treating the plants with the compounds and mixtures specifically indicated in the present text.
  • compositions or active compounds according to the invention can also be used to protect plants for a certain period after treatment against attack by the pathogens mentioned.
  • the period for which protection is provided generally extends over 1 to 28 days, preferably over 1 to 14 days, particularly preferably over 1 to 10 days, very particularly preferably over 1 to 7 days, after the treatment of the plants with the active compounds, or over up to 200 days after seed treatment.
  • Preparation and use of the active compounds of the formula (I) according to the invention is shown in the examples below. However, the invention is not limited to these examples.
  • This solid was dissolved in 150 mL of water and a 1M solution of hydrochloric acid was carefully added until pH reached 5. The resulting precipitated was filtered and dried to afford a green solid (5.3g). This solid was dissolved in ⁇ , ⁇ -dimethylformamide dimethylacetal (30 mL). The mixture was refluxed for 1 h. The solvant was evaporated. The residue was purified by colomn chromatography on silica gel (ethyl acetate) to afford 3.8 g of a brown solid.
  • the precipitate was filtered washed with water and dried overnight at 40°C under vacuum to afford 1 8.5 g of l -(5-Chloro-2-thienyl)-2-(pyrimidin-4- yl)ethanone which was used in the next step without further purification.
  • the resulting solid was dissolved in 95 mL of ⁇ , ⁇ -dimethylformamide dimethylacetal. The mixture was refluxed for lh30. After filtration of the precipitate, the solvant was evaporated.
  • N-Isopropyl-4-[3-(5-chloro-2-thienyl)-l-isopropyl-lH-pyrazol-4-yl]pyrimidin-2-amine A mixture of 4-[3-(5-chloro-2-thienyl)-l-isopropyl-lH-pyrazol-4-yl]-2-(methylsulfonyl)pyrimidine (leq, 0.39 mmol) in 2 mL isopropylamine was stirred overnight at room temperature.
  • N-Bromosuccinimide (leq, 0.38 mmol) was added to a solution of 4-[3-(5-chloro-2-thienyl)-lH- pyrazol-4-yl]pyridine (leq, 0.38 mmol) in 2 mL of NN-dimethylformamide. The mixture was then stirred at 80°C for 2h. Further N-Bromosuccinimide (0.3eq, 0.12 mmol) was added and the mixture was stirred for one more hour. After cooling to room temperature, ethyl acetate was added and the organic layer was washed with water, dried over MgS04, filtered and evaporated.
  • Trimethylboroxin 50% solution in THF, 1.3 mmol was then added and the mixture was stirred at 90 °C for 3 h. After cooling to room temperature, water and ethyl acetate were added. The aqueous layer was extracted with ethyl acetate and the combined organic extracts were washed with brine, dried over MgSO i, filtered and concentrated. The residue was dissolved in 3 mL of trifluoroacetic acid and stirred at 65 °C for 2 h. Water and ethyl acetate were added. And the aqueous layer was extracted with ethyl acetate.
  • the mixture was stirred for 5 mins at 160 °C in the microwave. After cooling to room temperature, the reaction mixture was diluted with water and ethyl acetate was added. The aqueous layer was extracted with ethyl acetate and the combined organic extracts were dried over MgSOi, filtered and concentrated. The residue was dissolved in 1 mL of trifluoroacetic acid and stirred at 65 °C for 2 h. Water and ethyl acetate were added. And the aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with a saturated solution of sodium hydrogen carbonate, dried over MgSOi, filtered and concentrated.
  • Tetrakis(triphenylphosphine)palladium (0) (0.055 eq, 0.036 mmol) was added to a degassed solution of 4- [5-bromo- 1 -(4-methoxybenzyl)-(3/5)-(5 -chloro-2-thienyl)- 1 H-pyrazol-4-yl]pyridine (1 eq, 0.65 mmol) and tributyl-l-propynylstannane (1.1 eq, 0.72 mmol) in 8 mL of acetonitrile. The mixture was then heated in the microwave at 150°C for 30 min. The mixture was filtered and evaportated.
  • 3-(2-thienyl)-lH-pyrazole (23.2 mmol) was dissolved in 100 mL dry NN-dimethylformamide and cooled to 0 °C under argon atmosphere.
  • Sodium hydride (28.0 mmol, 60% dispersion in mineral oil) was added in portions at 0 °C.
  • the reaction mixture was allowed to warm to room temperature and was stirred at room temperature for 15 min.
  • 2-iodobutane (35.0 mmol) was added dropwise at 0 °C.
  • the reaction mixture was stirred at room temperature for 14 h. Water and MTBE were added to the reaction mixture. The phases were separated and the aqueous phase was extracted with MTBE.
  • aqueous phase was extracted with ethyl acetate and the combined organic layers were successively washed with saturated aqueous ammonium chloride solution, saturated aqueous sodium bicarbonate solution and with brine, dried over MgSO i, filtered and concentrated to afford 864 mg of a mixture of l-methyl-5-propyl-3-(2-thienyl)-lH-pyrazole and l-methyl-3-propyl-5-(2-thienyl)- lH-pyrazole (90: 10) with some phosphine and phosphinoxide impurities.
  • Dry THF was degassed by purging the solvent with a continuous flow of argon for 15 min.
  • a microwave vial 10-20 mL of reaction volume
  • bis(triphenylphosphine)palladium(II) chloride (0.08 mmol)
  • copper(I) iodide (0.16 mmol)
  • 1 - Pentyne (4.0 mmol)
  • dry triethylamine 4.2 mmol
  • 3-methylthiophene-2-carbonyl chloride 4.0 mmol
  • reaction mixture was purged with argon and stirred for 2 h at room temperature under argon atmosphere.
  • 1 .5 mL Methanol, 1 .5 mL acetic acid and methylhydrazine (4.4 mmol) were added to the reaction mixture.
  • the microwave vial was capped with a septum and transferred to a laboratory microwave oven.
  • the reaction mixture was irradiated to a reaction temperature of 150 °C for 10 min (irradiation power: 50 to 230 W, pressure: 7-8 bar). After cooling to room temperature, the reaction mixture was concentrated under reduced pressure and dried in vacuum overnight. The residue was partitioned between MTBE and aqueous saturated sodium carbonate solution.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pretreatment Of Seeds And Plants (AREA)

Abstract

La présente invention concerne une thiénylpyri(mi)dinylazole de formule (I) dans laquelle R1 à R8 et X1 ont les significations données dans la description, et des sels agrochimiquement actifs, leur utilisation et des procédés et compositions pour lutter contre des champignons nocifs phytopathogènes dans et/ou sur des plantes ou dans et/ou sur des semences de plantes et pour réduire les mycotoxines dans les plantes et les parties des plantes. L'invention concerne également des procédés de préparation de tels composés et compositions, des semences traitées, et également leur utilisation pour lutter contre des champignons nocifs phytopathogènes dans le domaine agricole, horticole, forestier, dans l'élevage du bétail, dans la protection des matériaux, dans le domaine domestique et de l'hygiène et pour réduire les mycotoxines dans les plantes et les parties de plantes.
EP10790993A 2009-12-21 2010-12-20 Thiénylpyri(mi)dinylazole et utilisation associée dans la lutte contre des champignons phytopathogènes Withdrawn EP2516423A1 (fr)

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EP10790993A EP2516423A1 (fr) 2009-12-21 2010-12-20 Thiénylpyri(mi)dinylazole et utilisation associée dans la lutte contre des champignons phytopathogènes

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BR112012018358A2 (pt) 2016-08-09

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